00222151_130-S2_00222151_130-S2 06/05/16 12:05 PM Page 1

The Journal of
Laryngology & Otology VOLUME 130 MAY 2016 VOLUME 130 | NUMBER S2 | MAY 2016 ISSN: 0022-2151

Foreword S1

The Journal of Laryngology & Otology

Guidelines
Introduction to the United Kingdom National Multidisciplinary Guidelines for Head and Neck Cancer: V Paleri, N Roland
Organisation and provision of head and neck cancer surgical services in the United Kingdom: United Kingdom National Multidisciplinary Guidelines:
S3
The Journal of
F Stafford, K Ah-See, M Fardy, K Fell S5

Laryngology
Aetiology and risk factors for head and neck cancer: United Kingdom National Multidisciplinary Guidelines: R Shaw, N Beasley S9
Pre-treatment clinical assessment in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: A Robson, J Sturman,
P Williamson, P Conboy, S Penney, H Wood S13
Anaesthesia for head and neck surgery: United Kingdom National Multidisciplinary Guidelines: P Charters, I Ahmad, A Patel, S Russell S23
Imaging in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: H Lewis-Jones, S Colley, D Gibson S28
Nutritional management in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: B Talwar, R Donnelly, R Skelly, M Donaldson S32

& Otology
Restorative dentistry and oral rehabilitation: United Kingdom National Multidisciplinary Guidelines: C Butterworth, L McCaul, C Barclay S41
Psychological management for head and neck cancer patients: United Kingdom National Multidisciplinary Guidelines: G Humphris S45
Quality of life considerations in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: SN Rogers, C Semple, M Babb, G Humphris S49
Tumour assessment and staging: United Kingdom National Multidisciplinary Guidelines: N Roland, G Porter, B Fish, Z Makura S53
Pathological aspects of the assessment of head and neck cancers: United Kingdom National Multidisciplinary Guidelines: TR Helliwell, TE Giles S59
Radiotherapy in head and neck cancer management: United Kingdom National Multidisciplinary Guidelines: C Nutting S66
Surgery in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: JJ Homer S68
Chemotherapy: United Kingdom National Multidisciplinary Guidelines: CG Kelly S71
Laryngeal cancer: United Kingdom National Multidisciplinary guidelines: TM Jones, M De, B Foran, K Harrington, S Mortimore S75
Oral cavity and lip cancer: United Kingdom National Multidisciplinary Guidelines: C Kerawala, T Roques, J-P Jeannon, B Bisase S83
Oropharyngeal cancer: United Kingdom National Multidisciplinary Guidelines: H Mehanna, M Evans, M Beasley, S Chatterjee, M Dilkes, J Homer, Head and Neck Cancer:
J O’hara, M Robinson, R Shaw, P Sloan S90
Nasopharyngeal carcinoma: United Kingdom National Multidisciplinary Guidelines: R Simo, M Robinson, M Lei, A Sibtain, S Hickey S97
United Kingdom National Multidisciplinary Guidelines
Hypopharyngeal cancer: United Kingdom National Multidisciplinary Guidelines: P Pracy, S Loughran, J Good, S Parmar, R Goranova S104 Edited by Vinidh Paleri and Nick Roland
Nose and paranasal sinus tumours: United Kingdom National Multidisciplinary Guidelines: VJ Lund, PM Clarke, AC Swift, GW McGarry,
C Kerawala, D Carnell S111
Management of lateral skull base cancer: United Kingdom National Multidisciplinary Guidelines: JJ Homer, T Lesser, D Moffat, N Slevin,
R Price, T Blackburn S119
Non-melanoma skin cancer: United Kingdom National Multidisciplinary Guidelines: C Newlands, R Currie, A Memon, S Whitaker, T Woolford S125
Head and neck melanoma (excluding ocular melanoma): United Kingdom National Multidisciplinary Guidelines: OA Ahmed, C Kelly S133
ENDORSED BY:

VOLUME 130 | NUMBER S2 | MAY 2016

Management of Salivary Gland Tumours: United Kingdom National Multidisciplinary Guidelines: S Sood, M McGurk, F Vaz S142
Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines: AL Mitchell, A Gandhi, D Scott-Coombes, P Perros S150
Management of neck metastases in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: V Paleri, TG Urbano, H Mehanna, British Association of Endocrine and
C Repanos, J Lancaster, T Roques, M Patel, M Sen S161
Thyroid Surgeons (BAETS)
Investigation and management of the unknown primary with metastatic neck disease: United Kingdom National Multidisciplinary Guidelines: K Mackenzie,
M Watson, P Jankowska, S Bhide, R Simo S170
Speech and swallow rehabilitation in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: P Clarke, K Radford, M Coffey, British Association of Head and Neck
M Stewart S176
Recurrent head and neck cancer: United Kingdom National Multidisciplinary Guidelines: H Mehanna, A Kong, SK Ahmed S181
Oncologists (BAHNO)
Reconstructive considerations in head and neck surgical oncology: United Kingdom National Multidisciplinary Guidelines: M Ragbir, JS Brown, H Mehanna S191
Palliative and supportive care in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: H Cocks, K Ah–See, M Capel, P Taylor S198 British Association of Oral and
Follow-up after treatment for head and neck cancer: United Kingdom National Multidisciplinary Guidelines: R Simo, J Homer, P Clarke, K Mackenzie, Maxillofacial Surgeons (BAOMS)
V Paleri, P Pracy, N Roland S208
The clinical nurse specialist’s role in head and neck cancer care: United Kingdom National Multidisciplinary Guidelines: L Dempsey, S Orr, S Lane, A Scott S212
Clinical research, national studies and grant applications: United Kingdom National Multidisciplinary Guidelines: N Stafford S216 British Association of
Education of trainees, training and fellowships for head and neck oncologic and surgical training in the UK: United Kingdom National Otorhinolaryngology–Head and
Multidisciplinary Guidelines: R Simo, A Robson, B Woodwards, P Niblock, P Matteucci S218
Future perspectives: United Kingdom National Multidisciplinary Guidelines: EV King, K Harrington S222 Neck Surgery (ENT UK)

British Association of Plastic,

Reconstructive and Aesthetic Surgeons
(BAPRAS)

The Royal College of Pathologists

(RCPath)

The Royal College of Radiologists

(Faculty of Clinical Oncology) (RCR)
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00222151_130-S2_00222151_130-S2 06/05/16 12:05 PM Page 2
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 The Journal of

Laryngology & Otology

Volume 130, Number S2, March 2016

Head and Neck Cancer:

United Kingdom National Multidisciplinary Guidelines
Edited by:
Vinidh Paleri
Department of Otolaryngology-Head and Neck Surgery, The Newcastle Upon Tyne Hospitals
NHS Foundation Trust, Northern Institute of Cancer Research, Newcastle Upon Tyne
Nick Roland
Department of Otolaryngology-Head and Neck Surgery, Aintree University Hospitals
NHS Foundation Trust, Liverpool, UK

Endorsed by:

Sponsored by:

JLO (1984) Ltd

Publication of this Supplement was supported by JLO (1984) Ltd.

These guidelines have been reviewed by the Guest Editors and may be cited.
 The Journal of

Laryngology & Otology

Founded in 1887 by Morell Mackenzie and Norris Wolfenden

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The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S1–S2.
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116001195
On behalf of the British
Association of Endocrine and
Thyroid Surgeons, it is a pleasure
to endorse this multidisciplinary
document. BAETS represents
surgeons who have developed
particular expertise in thyroid
surgery, regardless of the spe-
cialty in which they originally trained. The inclusion
of thyroid cancer with upper airway cancers is pragmat-
ic because they share some common features clinically
at presentation, particularly the presence of a ‘lump’ in
the neck. The most recent British Thyroid Association
guidelines for the treatment of thyroid cancer cover the
investigation and management of thyroid cancer in
depth. BAETS maintains a huge database of outcomes
after surgery of the thyroid, both benign and malignant.
This satisfies the requirement for surgeons to collect
data in line with the requirements of HQIP.
Mark Lansdown BSc, MBBCh, MCh, FRCS
President
British Association of Endocrine and Thyroid Surgeons
The United Kingdom is a major
player in clinical and basic
science research into head and
neck cancer, but trying to
compare treatment methods is
fraught with difficulty, and there-
fore evidence for one treatment
over another is scarce. Due to the
complexity and rarity of head and
neck cancer, it has always been very difficult to decide
what the best treatment is as there are multiple elements
to the management.
In 2011, two brave souls decided that the time was
right to pull together the great and the good to
produce a UK Multidisciplinary Consensus Guideline
for Head and Neck Oncology, in an attempt to establish
best practice.
This has been the benchmark document for the man-
agement head and neck cancer in the UK on which to
base our MDT decisions. It was and continues to be
truly multidisciplinary.
Over time, treatments are evaluated, so in light of the
advances made in radiotherapy delivery and che-
motherapeutic options, as well as new technologies
e.g. transoral robotic surgery, the time is right to
relook at these guidelines and update them,
FOREWORD
The British Association of Head and Neck
Oncologists represents the multidisciplinary head and
neck community within the UK, so as President, I
offer once again the grateful thanks of our association
to both the editors and the many contributing authors
for their tireless efforts in compiling and publishing
this essential set of clinical guidelines.
Michael Fardy FFDRCSI, FDSRCS, FRCS
President
British Association of Head and Neck Oncologists
Guidelines are an essential part of
the process of ensuring appropriate
treatment is available and provided
for patients unfortunate enough to
be given a diagnosis of a head
and neck malignancy. There is a
need to make sure that these guide-
lines are regularly updated so that
our interventions remain up to date and effective, and I
am pleased that this has already taken place. As a max-
illofacial head and neck surgeon I have seen many
changes and improvements, but teamwork, respect and
co-operation with colleagues to smooth the patient
journey are paramount and have greatly improved. The
Liverpool group was lucky enough to have the opportun-
ity to host the European Congress on Head and Neck
Oncology in 2014, and demonstrate the high level of
team-working in the clinical and research arena. The
average head and neck cancer patient has a rocky path
to tread, and there is no doubt that such a publication
available to all will help them along the way.
Professor James S Brown MD FRCS FDSRCS
President
British Association of Oral and Maxillofacial Surgeons
It is a privilege to write a foreword
for this superb document. Once
again our head and neck collea-
gues have demonstrated great
collegiality and teamwork to
produce an outstanding consen-
sus document. It is also remark-
ably user friendly and I am sure
will provide a superb clinical resource for the benefit
of our patients. This approach along with improved
S2
data collection and analysis will help keep British
surgery at the forefront of care for many years ahead.
Professor Antony A Narula MA MB BChir FRCS
FRCS (Ed)
President
British Association of Otorhinolaryngology-Head &
Neck Surgery
It is fascinating to compare these
excellent, updated guidelines
with the old version. Doing so
unfolds a story of true multidis-
ciplinary care leading to improved
patient outcomes, where each
individual in a team knows that
they cannot function without the
others, and that everyone has skills and strengths to
add to the whole for the benefit of the patient under
the team’s care. As a result of that multidisciplinary
care, the treatment of head and neck cancer has
changed very much for the better in the last two
decades, and I commend those involved in treating
these patients for their dedication. In particular, the
head and neck surgeons deserve praise for being first
on board the National Flap Register, which is a testa-
ment to their desire to continuously improve care and
outcomes for this complex and heterogenous patient
population. Congratulations to all!
Mr Nigel Mercer FRCS
President, 2015–2016
British Association of Plastic, Reconstructive and
Aesthetic Surgeons
The Royal College of Pathologists
is delighted to endorse this publi-
cation and I would like to take
the opportunity to thank the
authors and editors for all their
hard work, particularly Professor
Helliwell and Dr Giles, who con-
tributed the pathology content.
FOREWORD
Members of all the contributing specialties are to be
congratulated on the degree of collaboration and con-
sensus reached and the high quality of the resulting
document. The latest version of these comprehensive
guidelines will support multidisciplinary teams
working in head and neck cancer and help them
provide the best possible outcome for patients.
Additions since the last edition include recent advances
in molecular pathology, particularly the development
of molecular evaluation for viral-induced cancers.
Such quality-assured pathology guidance provides
reassurance to clinical teams that pathology informa-
tion is based on good evidence and has the confidence
of pathologists across the UK. Congratulations on an
excellent document, which I’m sure will be welcomed
by members of all specialties working in this area.
Suzy Lishman FRCPath
President
The Royal College of Pathologists
On behalf of The Royal College
of Radiologists I very much
welcome the updating of these
important multidisciplinary
guidelines for head and neck
cancer. They provide a valuable
resource for all those across
many specialties who are
involved in the treatment of patients with head and
neck cancer and they should continue to be essential
reading. The guidelines cover all aspects of head and
neck cancer management, from epidemiology and diag-
nosis through to treatment and outcomes, and I
commend the editors and authors – a number of
whom are Fellows of the RCR – for this tremendous
body of work. I hope this new edition will continue to
encourage and support multidisciplinary working and
thereby help to improve patient care and ensure the
highest possible standards are achieved and maintained.
Dr Giles Maskell
President
The Royal College of Radiologists
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S3–S4. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000359

Introduction to the United Kingdom National

Multidisciplinary Guidelines for Head and Neck
Cancer

V PALERI1, N ROLAND2
1
Department of Otolaryngology-Head and Neck Surgery, The Newcastle Upon Tyne Hospitals NHS Foundation
Trust, Northern Institute of Cancer Research, Newcastle Upon Tyne, and 2Department of Otolaryngology-Head
and Neck Surgery, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK

Abstract
This is the 5th edition of the UK Multi-Disciplinary Guidelines for Head and Neck Cancer, endorsed by seven
national specialty associations involved in head and neck cancer care. Our aim is to provide a document can be
used as a ready reference for multidisciplinary teams and a concise easy read for trainees. All evidence based
recommendations in this edition are indicated by ‘(R)’ and where the multidisciplinary team of authors consider
a recommendation to be based on clinical experience, it is denoted by ‘(G)’ as a good practice point.

It is an enormous privilege and a great pleasure to intro-
duce the 5th edition of the UK Multi-Disciplinary
Guidelines for Head and Neck Cancer. Akin to the
4th edition,1 each aspect of the guideline has been
developed by an expert team, often multidisciplinary.
An affirmation of the true multidisciplinary nature of
these guidelines is the endorsement by seven medical
specialty organisations involved in head and neck
cancer care in the UK: British Association of
Endocrine and Thyroid Surgeons, British Association
of Head and Neck Oncologists, British Association of
Oral and Maxillofacial Surgeons, British Association
of Otorhinolaryngology-Head and Neck Surgery,
British Association of Plastic, Reconstructive and
Aesthetic Surgeons, The Royal College of Pathologists
and The Royal College of Radiologists (Faculty of
Clinical Oncology). The guidelines will be of interest
across the spectrum of healthcare professionals who
look after patients with Head and Neck Cancer.
Our aim was to produce multidisciplinary consensus
recommendations on the management of Head and
Neck cancer based on the expertise and experience
invested within the UK-based international experts
and their appraisal of the current evidence. The remit
of these guidelines is to provide evidence-based recom-
mendations that will help identify an optimal manage-
ment strategy. It should be appreciated that the ultimate
decision for the management should rest with the
multidisciplinary team, which takes into account all
clinical data pertaining to the patient and his or her
own social circumstances and individual preferences.
In contrast to the 4th edition, we have migrated away
from the Scottish Intercollegiate Guidelines Network
(SIGN) grading of recommendations. In 2013, SIGN
abandoned its ABCD grading method2 as it became
evident that not all research would fit within the
constraints of this system. Scottish Intercollegiate
Guidelines Network has since adopted the system
developed by the Grading of Recommendations
Assessment, Development and Evaluation (GRADE)
working group.3 Having studied the GRADE method-
ology in detail, we concluded that a guideline such as
this, generated by a multidisciplinary group of practis-
ing clinicians, simply did not possess the resources and
the time to use the GRADE methodology. Similar to
some of the more recent SIGN guidelines, all evi-
dence-based recommendations in this edition come
without a grade attached, indicated by ‘(R)’ and
where the multidisciplinary team of authors consider
a recommendation to be based on clinical experience,
it is denoted as a good practice point ‘(G)’.
The 5th edition will again provide a robust clinical
document, which can be used as a ready reference.
and a concise easy read for trainees and all involved
in Head and Neck cancer care. In conjunction with
the upper aerodigestive tract cancer guidelines pub-
lished recently by the National Institute for Health
and Care Excellence,4 the recommendations across
these two publications should improve the care pro-
vided to this complex disease. The tremendous amount
of work put in by the authors is being recognised by
individually indexed publications; however, we would
recommend that readers use this supplement in the
Journal of Laryngology and Otology as a single docu-
ment owing to the cross-referencing within it. We are
confident that the publication of the 5th edition as a
S4
journal supplement will enhance readership and facili-
tate greater dissemination across the Head and Neck
community.
Acknowledgements
We would like to express our deepest gratitude to the col-
leges, societies and representatives that have made this pos-
sible and most of all for the generous time contributed by
the authors of each subject topic. We are indebted to Aled
Hills and the team at Cambridge University Press for their
exceptional diligence, and the Trustees of JLO (1984) Ltd
for their generous support.
References
1 Roland NJ, Paleri V, eds. Head and Neck Cancer: Multidisciplinary
Management Guidelines, 4th edn. London: ENT UK, 2011
V PALERI AND N ROLAND
2 Scottish Intercollegiate Guidelines Network (SIGN). Methodo-
logical principles. http://www.sign.ac.uk/methodology/index.html
(accessed 15 October 2015)
3 Grading of Recommendations Assessment, Development and
Evaluation Working Group. http://www.gradeworkinggroup.
org/ (accessed 15 October 2015)
4 National Institute for Health and Care Excellence. Cancer of the
upper aerodigestive tract: assessment and management in
people aged 16 and over. London: National Institute for Health
and Care Excellence, 2016. https://www.nice.org.uk/guidance/
ng36 (accessed 27 April 2016)
Address for correspondence:
Vinidh Paleri,
Department of Otolaryngology-Head and Neck Surgery,
The Newcastle upon Tyne Hospitals NHS Foundation Trust,
Northern Institute of Cancer Research,
Newcastle Upon Tyne, UK.
E-mail: vinidh.paleri@ncl.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S5–S8. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000839

Organisation and provision of head and neck cancer

surgical services in the United Kingdom: United
Kingdom National Multidisciplinary Guidelines

F STAFFORD1, K AH-SEE2, M FARDY3, K FELL4

1
Sunderland Royal Hospital, Sunderland, 2Department of Otolaryngology – Head and Neck Surgery, Aberdeen
Royal Infirmary, Aberdeen, UK, 3University Hospital of Wales, Cardiff, UK, and 4NHS England (Midlands and
East), CNS Tumours and Head and Neck Cancers, UK

Abstract
This is the official guideline endorsed by the surgical specialty associations involved in the care of head and neck
cancer patients in the UK. This paper summarises the current state of play in the organisation and provision of
head and neck cancer surgical services in the UK.

Introduction recommendations in the Health and Social Care Act

The quality and availability of care for patients with head
2012.5 This is the fifth major reorganisation of the
and neck cancer has improved immeasurably over the
NHS structure since 2000. Primary Care Trusts and
past 30 years. Improved training, application of evidence-
Strategic Health Authorities were disbanded and replaced
based practice, multi-disciplinary working, improved sur-
with 211 Clinical Commissioning Groups (CCGs) made
gical and radiation techniques, chemotherapy, public
up of local GPs covering populations of over 250 000
health education, subspecialisation and in particular the
under the umbrella of The NHS Commissioning Board,
National Institute for Health and Care Excellence (NICE)
which became NHS England and began functioning on
Improving Outcomes guidelines,1 the previous editions
1st April 2013. Clinical Commissioning Groups do not
of the Multidisciplinary Head and Neck Cancer guide-
commission GP or specialised services as these are direct-
lines2 and peer review have all played their part. Despite
ly commissioned.6 Some services have been designated
this, the availability of some treatment options and survival
as ‘specialised’ and based upon principles laid out in
outcomes in the UK still seem to lag behind other Western
the Carter Report and the Department of Health white
countries. Further improvement is required but the finan-
paper ‘Equity and excellence: liberating the NHS’.7 In
cial constraints in the National Health Service (NHS), high-
addition, a structure for prescribing and identifying
lighted over recent months, could overwhelm us and
these services is now in place.
consequently could affect progress in developing clinical
NHS England became responsible for directly
services for the foreseeable future.
commissioned services (including specialised services)
Since the inception of the NHS, healthcare spending
in April 2013 (Scotland and Wales have their own com-
in the UK has increased 4 per cent per year. In 1960, it
missioning structures). This structure is currently under
was less than 5 per cent of gross domestic product
review and many of the designated specialised services
(GDP), 50 years on it is now about 10 per cent of
may have commissioning devolved to the CCGs. The
GDP. Current estimates suggest that within 10 years,
NHS England website defines specialised services as
unchecked healthcare spending will outstrip economic
those provided in relatively few hospitals, accessed by
growth and is not sustainable, and by 2050 spending
comparatively small numbers of patients but with catch-
would increase to over 20 per cent of GDP.3 The
ment populations of usually more than 1 million. These
Five Year Forward View, published in October
services tend to be located in specialised hospital trusts
2014,4 describes ways in which the NHS intends to
that can recruit a team of staff with the appropriate
tackle the exponential rises in the cost of NHS services.
expertise and enable them to develop their skills.
Specialised services account for approximately 14 per
Commissioning healthcare services cent of the total NHS budget, about £13.8 billion per
annum. The commissioning of specialised services is a
England prescribed direct commissioning responsibility of NHS
Commissioning of healthcare in all its aspects under- England. The manual for prescribed specialised services
went a total organisational restructuring based upon 2013/2014 identifies 143 services.8
S6
A description of the new structure for commission-
ing specialised services is given in detail on the NHS
England website. Commissioning has been devolved
to six programmes of care (POC) each with its own
team of commissioners:
• internal medicine
• cancer
• blood and infection
• mental health
• trauma
• women and children.
The national Cancer and Blood POC covers the pre-
scribed specialised services in infection, cancer, immun-
ity and haematology. This relates to both specialised and
highly specialised prescribed services, and includes both
surgical and medical services. There are 74 specialist ser-
vices within the POC, and these are clustered into Clinical
Reference Groups (CRGs) to support the national work in
these areas. The Cancer Programme of Care covers some
of the prescribed specialised and highly specialised ser-
vices. Complex head and neck is one of 17 specialised
services in the Cancer and Blood Programme. These
service-specific CRGs also work with other CRGs
where key service interfaces and interdependencies
between CRG areas occur. A public consultation to amal-
gamate CRGs is currently underway; the impact for head
and neck surgery will be the creation of a super CRG that
includes all of cancer surgery.
The CRG for a specific specialty will advise the
designated commissioners on service standards and
requirements, and will complete designated tasks
requested by the commissioners. Each CRG consists
of a chair and members (up to 15) consisting of repre-
sentatives from the 12 Clinical Senates, relevant profes-
sional organisations and patient groups. England has
been divided into 12 Clinical Senates similar (but not
identical) geographically to the new Cancer Networks
providing members for the different CRGs. More infor-
mation is available on the NHS England website
(http://www.england.nhs.uk/ourwork/part-rel/cs/)
The Complex Head and Neck Clinical Reference
Group (HNCRG) covers complex benign and malig-
nant head and neck services and refers to a group of
very different tumours, including oral (mouth, lip
and oral cavity), larynx, pharynx, thyroid and saliv-
ary glands tumours amongst others. It may become
the responsibility of the CRGs to advise specialised
commissioners and NHS England on ways to
improve efficiency and reduce costs without affect-
ing quality or provision of care. An example is the
NHS England policy on Transoral Robotic Surgery
that has been developed under the aegis of the
CRG which is undergoing public consultation at
the time of this paper going to press. The apparent
poor comparisons with other European cancer
outcome audits and a wide national variation in pro-
vision of services and outcomes have become
F STAFFORD, K AH-SEE, M FARDY et al.
powerful drivers for political intervention and
change. Thus, over the past 10 years many providers
in England have moved towards some forms of cen-
tralisation model in response to the National Institute
for Health and Care Excellence (NICE) improving
outcomes guidance (IOG) for head and neck
cancers, although this is not universal.
Potentially, the HNCRG can have a great deal of
influence on the future structure of services nationally
by setting clear standards to the commissioners who
control the funding. To influence this process, readers
to contact their respective senate representative.
More information about CRGs is available from the
NHS England website. http://www.england.nhs.uk/
ourwork/commissioning/spec-services/npc-crg/
Scotland
The NHS in Scotland is a devolved service run by the
Scottish government out of parliament in Edinburgh. It
is delivered by 14 Regional Health Boards that cover
the disparate geography of Scotland. The Scottish
NHS budget is approximately £11.9 billion
(2013–2014 budget).
Head and neck cancer services are delivered by the
three major Cancer Networks within Scotland: North
of Scotland cancer network (NOSCAN), South of
Scotland (SCAN) and West of Scotland (WOSCAN).
These cancer networks work closely together to
provide a full and comprehensive head and neck
cancer service to the estimated 5.5 million population
in Scotland which is spread across a wide range of geo-
graphic areas from dense urban to remote and rural
sites. Over 1100 new cases of head and neck cancer
are diagnosed in Scotland per year.
In Scotland, commissioning groups have not been
introduced in the same way as in England and the deliv-
ery of the NHS in Scotland still follows the traditional
NHS method of GP referral to the local secondary care
centre with ‘urgent suspicion of cancer’ referral guide-
lines published by NHS Scotland in place. This sets the
standard of 62 days from referral to treatment for cancer
cases (http://www.healthcareimprovementscotland.
org/our_work/cancer_care_improvement/programme_
resources/scottish_referral_guidelines.aspx).
Quality improvement processes are in place in
Scotland including the introduction of quality perform-
ance indicators (QPIs) to set the standards for cancer
care within all cancer groups including head and neck
cancer. The QPIs have been developed collaboratively
with the three Regional Cancer Networks (NOSCAN,
SCAN, WOSCAN), Information Services Division
and Healthcare Improvement Scotland. The Scottish
Government has asked Healthcare Improvement
Scotland to provide performance assurance against
cancer QPIs and to publish their findings on a three
yearly basis (http://www.healthcareimprovementscot-
land.org/our_work/cancer_care_improvement/cancer_
qpis.aspx).
ORGANISATION AND PROVISION OF HEAD AND NECK CANCER SERVICES IN THE UK: UK GUIDELINES
The NHS funding constraints may make it necessary
to review the role of the currently designated cancer
centres in Scotland in the future.
Wales
The NHS England has identified head and neck surgery
as a speciality requiring specific funding arrangements.
The organisation and provision must be based in centres
covering a large population with an adequate workload.
Over the past 10 years many providers have moved
towards some forms of centralisation model in response
to the NICE IOG, although this is not universal.
All seven health boards in Wales offer head and neck
cancer services, irrespective of numbers; despite an exten-
sive review in 2009 attempting to rationalise services, this
has never happened. The existing regional service provi-
sion and local geographical and population factors will of
course impact on practical arrangements, but trusts will
be expected to justify the service structure with robust
data. As yet it is not clear if the CRG recommendations,
when they are published, will be accepted in Wales and
how they will be enforced. It is clear that there will be no
increase in funding and only measures which reduce or sta-
bilise costs are likely to be adopted. Head and neck cancer
surgical service providers should review their service pro-
vision as and when new guidance is published, but no statu-
tory authority exists to enforce these guidelines.
Cost of head and neck cancer care
Head and neck cancer is expensive to manage. In the
USA, it has been suggested that it is the most expensive
cancer to treat and patients rarely return to a productive
life, with estimated costs of $96 000–$150 000 for
multimodality treatment (surgery, chemotherapy and/
or radiotherapy).
The UK head and neck surgical services initially
developed within ENT and Oral and Maxillofacial
(OMF) departments without the introduction of
funding and were bundled in with other routine non-
oncologic surgical procedures and paid for through
local commissioning. Devolvement of services, central-
isation and specialisation mean this model cannot con-
tinue. Cost estimates for surgery with reconstruction
range in the UK and Europe from £25 000 to £30 000
and it is unclear in many units exactly how much of
the true cost is reimbursed by current tariffs based on
the health resource group codes. We need to be able
to quantify the financial impact of CRG advice regard-
ing changes to clinical practice and in order to do this,
more clear and more reliable coding and costing is
required to understand the viability of services in the
future and to monitor the financial effects of change.
Caseload and service provision
It is generally accepted, with some evidence, that patients
requiring complex surgical and oncological treatments
have better outcomes and the service is more efficient
when carried out in larger centres with specialist sur-
geons and oncologists. It has already been shown that
S7
there is a huge variation nationally in basic measures
such as in-hospital mortality and complications which
are unacceptable and a major factor in driving change.
The NICE guidance defines a minimum of 100 new
cases per year to be a credible provider. The previous
edition of the Multidisciplinary Head and Neck Cancer
guidelines suggested a higher number, over 250, to gen-
erate enough operative cases to develop and maintain
skills, provide a suitable training and research environ-
ment and allow a sufficient number of qualified surgeons
to provide adequate 24 hour, 7 days a week services.
When the 4th edition of these guidelines were pub-
lished in 2011,2 there were 33 cancer networks, with 69
multidisciplinary teams (MDTs) and 79 hospital provi-
ders. The 2012 Data for Head and Neck Oncology audit
reported 28 MDTs in England, 2 in Wales with 64
service providers for 8272 new cases. Of these providers,
14 reported fewer than 50 new cases per year and a further
11, fewer than 100 new cases. The other units mostly
report 150–180 cases, with six providers reporting more
than 200 cases per year. There is some under reporting
in these numbers due to failure to identify a provider,
but the picture is clear. There are units providing head
and neck services with relatively low numbers. Trusts
and individual surgeons should be examining the sustain-
ability of such service provision outside larger centres.
While geographical and public transport issues exist, the
CRG agrees with the NICE recommendations for Head
and Neck Centres to serve populations of over a million
or more. Within England, the CRG’s view is that cancer
centres should have a case load of at least 250 cases per
year, using a regional hub and spoke structure, with cen-
tralised surgeryand peripheral clinic and support services.
Currently, NHS England, in conjunction with National
Cancer Intelligence Network, is undertaking an audit of
current cancer service provision in England; thus no
recommendations will be forthcoming until the audit
and the restructuring of the CRG is complete.
Sir Bruce Keogh announced on 16th November
2014 the findings of a forum on provision of a 24 hour,
7 days a week health service, which will filter through
to head and neck services eventually (http://www.
nhsiq.nhs.uk/improvement-programmes/acute-care/
seven-day-services.aspx) and such reorganisation will
help with the planned 7-day health service.
Keys to the successful management of HNC are the
specialist nursing, speech and language, dietetics and
social support that these patients require. Easy and
ready access locally is essential. To counterbalance the
move to concentrate specialist surgery (radiotherapy is
by its nature centralised already) local provision of cen-
trally guided support units and visiting consultant clinics
should mitigate some of the patient concerns about dis-
tance from the surgical unit.
Surgical numbers
Individual surgeon reporting is not a concept that is
useful or valid in determining outcomes in head and
neck surgical practice. However, better outcome
S8
measures are on the way and accurate data collection and
publication from providers will be required to justify
funding, allow comparison with other centres and high-
light problems more quickly. Data collection is still poor
and undervalued by many hospital managers trying to
trim budgets, but the value of accurate validated data
cannot be underestimated and it should not be left to
busy clinicians to coordinate or enter data but to properly
trained and motivated data managers.
Surgeons’ operative numbers is always a thorny
question. The peer review process for thyroid surgery
adopted the British Association of Endocrine and
Thyroid Surgeons guideline of at least 20 thyroidec-
tomies per year as one of its markers and this is
likely to be expanded to some of the more common
head and neck procedures; examples include neck dis-
section, oral cancer resection, laryngectomy and free
flap reconstruction. There is no real evidence base to
determine how many particular procedures should be
recommended, but less than five major procedures
per year at a centre is not sustainable and a service
review is mandatory. Unusual procedures such as cra-
niofacial resection will be restricted even further to a
small number of nationally recognised centres.
Funding
As part of the Five Year Forward View, the commission-
ing of specialised services will assess the opportunities for
co-commissioning across all specialised services in order
to maximise all service elements associated with the
patients’ pathway and the provision of services to meet
the needs of patients. The national service specifications
and other commissioning products will provide a frame-
work through which specialised services can be defined
to ensure that services are delivered to national standards.
At the time of writing it is not clear what, if any, changes
will occur that could affect the commissioning of complex
head and neck cancer surgery. At present the commission-
ing of these services sits within the remit of specialised
commissioning, directly commissioned by NHS
England. The remaining services are funded by CCGs.
At the start of the specialised commissioning process
in 2013, it was clearly stated that the commissioning of
these services would be placed in the hands of specialised
commissioners, giving the opportunity to ensure that the
service delivered was in accordance with the published
service specification to ensure equity of access to high-
quality services across the country and to aid the smooth-
ing out variations in outcomes noted in cancer audits.
There was also a clear belief that this would also drive
a more efficient use of funds by providers, potentially a
cost reduction through larger services leading to a critical
mass of patients supported by an appropriate and cost-
effective infrastructure improving the quality and cost-
effectiveness in line with the NICE IOG.
Wholesale restructuring of regional services is rarely
achievable without cost. This will not be easy and it
seems to have stalled the process. Also, such changes
are often unwelcome in larger more sparsely populated
F STAFFORD, K AH-SEE, M FARDY et al.
geographical areas, although evidence would suggest
that it is clinicians and providers who provide the
most resistance; patients when questioned more often
express a desire to go to the expert centre.
Summary
Complex head and neck surgery has been commis-
sioned as a specialised service by NHS England. The
organisation and provision must be based in centres
covering a large population with an adequate workload.
Over the past 10 years many providers have moved
towards some form of centralisation model in response
to the NICE IOG, although this is not universal. This is
the driver for the work of the CRG, which intends to
undertake an audit of the current head and neck services
to explore whether the configuration in place meets
national IOG requirements and that there is a consistent
picture of delivering good outcomes to patients. The
view of the CRG is that more centralisation is required.
The existing regional service provision and local geo-
graphical and population factors will of course impact on
practical arrangements, but trusts will be expected to
justify the service structure with robust data. As yet it is
not clear if the CRG recommendations will be accepted
and how they will be enforced. It is clear that there will
be no increase in funding and only measures which
reduce or stabilise costs are likely to be adopted. Head
and neck cancer surgical service providers should con-
sider their current service provision and assess and con-
sider the potential impact of changes to future guidelines.
References
1 National Institute for Health and Care Excellence. Improving
Outcomes in Head and Neck Cancers – The Manual. London:
National Institute for Health and Care Excellence, 2004. http://
guidance.nice.org.uk/CSGHN [accessed 19 March 2015]
2 Roland NJ, Paleri V, eds. Head and Neck Cancer: Multidisciplinary
Management Guidelines. 4th edn. London: ENT UK, 2011
3 Appleby J. Spending on Health and Social Care over the Next 50
Years. Why Think Long Term? London: The King’s Fund, 2013.
http://www.kingsfund.org.uk/sites/files/kf/field/field_publi-
cation_file/Spending%20on%20health%20...%2050%20year-
s%20low%20res%20for%20web.pdf [accessed 19 March 2015]
4 NHS England. The NHS Five Year Forward View. 2014. http://
www.england.nhs.uk/wp-content/uploads/2014/10/5yfv-web.
pdf [accessed 19 March 2015]
5 Health and Social Care Act 2012. http://www.legislation.gov.
uk/ukpga/2012/7/contents/enacted [accessed 19 March 2015]
6 Department of Health. Review of Commissioning Arrangements for
Specialised Services. May 2006. http://webarchive.nationalarc-
hives.gov.uk/+/www.dh.gov.uk/en/Managingyourorganisation/
Commissioning/Commissioningspecialisedservices/DH_4135174
[accessed 19 March 2015]
7 Department of Health. Equity and Excellence: Liberating the NHS.
2010. https://www.gov.uk/government/uploads/system/uploads/
attachment_data/file/213823/dh_117794.pdf [accessed 19 March
2015]
8 NHS England. Manual for prescribed specialised services for 2013/
14. http://www.england.nhs.uk/wp-content/uploads/2014/01/
pss-manual.pdf [accessed 19 March 2015]
Address for correspondence:
Francis Stafford,
Sunderland Royal Hospital,
Sunderland, UK
E-mail: frankstafford@btinternet.com
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S9–S12. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000360

Aetiology and risk factors for head and neck

cancer: United Kingdom National Multidisciplinary
Guidelines

R SHAW1, N BEASLEY2
1
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of
Liverpool, Aintree University Hospitals NHS Foundation Trust, Liverpool, and 2Department of Otolaryngology –
Head and Neck Surgery, Nottingham University Hospitals NHS Trust, Nottingham, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. It discusses the aetiology and risk factors for head and neck cancer and the recommended
interventions appropriate for each risk factor.

Recommendations
• Recent evidence synthesis from National Institute for Health and Care Excellence suggests that the following brief inter-
ventions for smoking cessation work should be used:
○ Ask smokers how interested they are in quitting (R)
○ If they want to stop, refer them to an intensive support service such as National Health Service Stop Smoking Services (R)
○ If they are unwilling or unable to accept a referral, offer a stop smoking aid, e.g. pharmacotherapy. (R)
• Brief interventions are effective for hazardous and harmful drinking. (R)
• Specialist interventions are effective in people with alcohol dependence. (R)
• Most people with alcohol dependence can undergo medically assisted withdrawal safely at home, after risk assessment. (R)
• Management of leukoplakia is not informed by high-level evidence but consensus supports targeted use of biopsy and histo-
pathological assessment. (R)
• The management of biopsy proven dysplastic lesions favours:
○ advice to reduce known environmental carcinogens such as tobacco and alcohol (R)
○ surgical excision when the size of the lesions and the patient’s function allows (R)
○ long-term surveillance. (R)
• Fanconi anaemia patients should:
○ be followed up in a multidisciplinary specialist Fanconi anaemia clinic (G)
○ have quarterly screening for head and neck squamous cell carcinoma and an aggressive biopsy policy (G)
○ receive prophylactic vaccination against high risk human papilloma virus (G)
○ receive treatment for head and neck squamous cell carcinoma with surgery alone where possible. (G)

Introduction
The major risk factors for head and neck cancer in the
UK are tobacco smoking and alcohol consumption
and withdrawal of these environmental carcinogens
remains the focus for primary and secondary prevention.
Additionally the role of human papilloma virus (HPV) is
being increasingly recognised, but as the natural history
and transmission of oral and oropharyngeal HPV infec-
tion are incompletely understood, the opportunities for
reducing this risk are not yet clear. Some patients have
recognised local or systemic pre-malignant conditions
which are also discussed.
Smoking
Smoking is an independent risk factor for head and
neck cancer.1 Patients who continue to smoke during
radiotherapy are more likely to develop osteo-
radionecrosis and to require hospitalisation during
treatment. Continued smoking through radiotherapy
was thought to have an adverse effect on local
control (hazard ratio 1.5) and survival (hazard ratio
1.7), but more recent evidence would suggest baseline
smoking status is more important.2 Smoking cessation
before surgery is desirable to reduce the risk of anaes-
thetic related complications and improve wound
healing, particularly after reconstructive surgery.3,4
Quitting tobacco smoking for a short period of time
(one to four years) results in a head and neck cancer
risk reduction of about 30 per cent compared with
current smoking, reduces the risk of laryngeal cancer
by 60 per cent after 10–15 years and after 20 years
S10
can reduce the risk of developing oral cavity cancer to
the level of a never smoker.5
Recommendations
• Recent evidence from NICE suggests that the
following brief interventions for smoking
cessation work should be used:
○ Ask smokers how interested they are in
quitting (R)
○ If they want to stop, refer them to an
intensive support service such as NHS Stop
Smoking Services (R)
○ If they are unwilling or unable to accept a
referral, offer a stop smoking aid, e.g.
pharmacotherapy (R)
Alcohol
Alcohol is the other major independent risk factor for
head and neck cancer. Patients who continue to drink
heavily after treatment for head and neck cancer have
a significantly worse quality of life6 and continued
drinking has a negative impact on survival (hazard
ratio 1.28).7,8 The beneficial effects of quitting
alcohol, on the risk of developing head and neck
cancer, are only observed after more than 20 years,
when the level of risk reaches that of non-drinkers.5
Cessation of alcohol on admission for surgery can
present a significant problem in heavy drinkers. A
review in the British Medical Journal suggests that
we should screen all patients for excessive alcohol con-
sumption with a validated questionnaire such as Fast
Alcohol Screening Test.9
Recommendations
• Brief interventions are effective for hazardous
and harmful drinking (R)
• Specialist interventions are effective in people
with alcohol dependence (R)
• Most people with alcohol dependence can
undergo medically assisted withdrawal safely
at home, after risk assessment (R)
Human papilloma virus
Human papilloma virus -16 is an increasingly relevant
causative agent in oropharyngeal and oral squamous
cell carcinoma (SCC), however doubt remains in
other sites and for other HPV subtypes. Combined
data from recently published (2006–2009) studies
shows that 55 per cent of 654 oropharyngeal SCC
cases were HPV-16 positive.10 The prevalence of
HPV-16 chronic infection in oropharyngeal mucosa
of the general population is currently unclear.
R SHAW AND N BEASLEY
Without a clinically identifiable premalignant lesion,
any future (primary or secondary) screening approach
would rely on molecular biomarkers. Oral HPV infec-
tion increases with numbers of recent oral sex partners
and isolated cases of transmission of HPV-16 between
partners leading to the possible ‘transmission’ of
cancer have been reported.11 Evidence seems currently
insufficient to counsel avoidance of specific sexual
activities, over and above guidance that informs the
prevention of other sexually transmitted diseases. It is
awaited with interest as to whether the current pro-
gramme of vaccination against high risk HPV (strains
16 and 18) offered to 12–13-year-old girls will in the
future reduce the incidence of head and neck squamous
cell carcinoma (HNSCC).
Premalignant lesions
Leukoplakia and erythroplakia are common premalig-
nant lesions; however, most HNSCC cases have no
history of such antecedent lesions. Biopsy-proven epi-
thelial dysplasia is demonstrated in 25 per cent of biop-
sies of leukoplakia but most erythroplakia; however,
HPV-16 is very rarely a factor in these conditions.
The significant clinical predictors of malignant trans-
formation in oral dysplastic lesions are non-smoking
status, sub-site (e.g., high risk in lateral tongue and
low risk in floor of mouth), non-homogeneous appear-
ance, size of lesion greater than 200 mm and higher
histological grade (severe vs mild/moderate). A
recent systematic review of oral dysplasia (992
patients) showed malignant transformation in 12.1 per
cent after mean 4.3 years following biopsy.12 Severity
of dysplasia predicted for malignant transformation
( p = 0.008). Lesions that were not excised demon-
strated considerably higher transformation rate than
those that were excised ( p = 0.003).13 A binary histo-
logical grading into the high and low risks has been
suggested based on good predictive power that has
been independently verified in other series. A system-
atic review of laryngeal dysplastic lesions (942
patients) showed transformation in 14 per cent after a
mean interval of 5.8 years, again severity of dysplasia
correlated with risk of transformation.14
Importantly, these data only reflect patients already
referred for a specialist opinion and with biopsy-
proven dysplasia. In population-based studies of oral
leukoplakia without histological inclusion criteria the
risks are much lower; 40–50 per cent regress spontan-
eously and less than 1 per cent transform.15,16 There is
insufficient evidence to justify screening in the general
population to prevent oral cancer.17
The premalignant potential of oral lichen planus
(OLP) is controversial; however, rigorously conducted
retrospective series have confirmed the risk in classic
inflammatory OLP with histological confirmation is
low, at about 1 per cent. Oral lichenoid lesions which
harbour features of OLP, but also epithelial dysplasia
do present a modest risk for malignant transformation,
and in some series this subset reflect the only cancer
AETIOLOGY AND RISK FACTORS FOR HEAD AND NECK CANCER: UK GUIDELINES
cases arising, interestingly with a predisposition to
lateral tongue. Proliferative verrucous leukoplakia is a
rare condition presenting with exophytic widespread
progressive leukoplakia, somewhat refractory to inter-
vention and with very high (50–80 per cent) transform-
ation rates and hence, poor overall prognosis.
Recommendations
• Management of leukoplakia is not informed
by high-level evidence, but consensus
supports targeted use of biopsy and
histopathological assessment (R)
• The management of biopsy proven dysplastic
lesions favours:
○ advice to reduce known environmental
carcinogens such as tobacco and alcohol
(R)
○ surgical excision when the size of the
lesions and the patient’s function allows
(R)
○ long-term surveillance (R)
Premalignant conditions
Inherited
Inherited conditions with increased risk of HNSCC
include Fanconi anaemia (FA), ataxia telangiectasia,
Bloom’s syndrome and Li–Fraumeni syndrome.
Fanconi anaemia has a very high risk of developing
HNSCC (particularly oropharyngeal squamous cell
carcinoma), most notably after haematopoietic stem
cell transplantation.18 Recent evidence suggests a
possibility that HPV may be implicated in FA-related
oropharyngeal squamous cell carcinoma.19 Fanconi
anaemia patients do not tolerate cisplatin and have
severe toxicity with radiotherapy. Life expectancy has
improved so that the population at risk for HNSCC is
greater. Head and neck squamous cell carcinoma can
occur early in patients as young as 11 years old.
Further guidance is available from http://www.fanco-
nianaemia.nhs.uk
Recommendation
• Fanconi anaemia patients should:
○ be followed up in a multidisciplinary
specialist FA clinic (G)
○ have quarterly screening for HNSCC and
an aggressive biopsy policy (G)
○ receive prophylactic vaccination against
high risk HPV (G)
○ receive treatment for HNSCC with surgery
alone where possible
S11
Acquired immunodeficiency
Patients who are immunosuppressed due to poor nutri-
tion, advanced age, immunosuppressive therapy after
transplant or acquired immunodeficiency syndrome
(AIDS) are at greater risk of developing malignancy.
The most commonly reported AIDS-related neoplasms
of the head and neck region include Kaposi’s sarcoma
and non-Hodgkin’s lymphoma. There is also an
increased risk of oropharyngeal squamous cell carcin-
oma. Although HPV-related HNSCC has been seen
in immunosuppressed patients, further clinical studies
are needed to determine the safety and effectiveness
of HPV vaccines in this setting.
Key points
• Smoking is an independent risk factor for head
and neck cancer, is associated with post treatment
complications and has an adverse effect on onco-
logical outcomes
• Alcohol is an independent risk factor for head and
neck cancer and continued drinking has a negative
impact on survival
• High risk human papilloma viruses (HPV 16 and
18) are recognised causative agents for oropharyn-
geal squamous cell carcinoma
• Malignant transformation of oral dysplasia and
laryngeal dysplasia occurs in 12 per cent (mean
4.3 years) and in 14 percent (mean 5.8 years)
respectively.
References
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Schouten LJ. Alcohol consumption, cigarette smoking and the
risk of subtypes of head-neck cancer: results from the
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2 Zevallos JP, Mallen MJ, Lam CY, Karam-Hage M, Blalock J,
Wetter DW et al. Complications of radiotherapy in laryngophar-
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program. Cancer 2009;115:4636–44
3 Tang MW, Oakley R, Dale C, Purushotham A, Moller H,
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smoking.pdf (accessed 15 November 2015)
5 Marron M, Boffetta P, Zhang ZF, Zaridze D, Wunsch-Filho V,
Winn DM et al. Cessation of alcohol drinking, tobacco
smoking and the reversal of head and neck cancer risk. Int J
Epidemiol 2010;39:182–96
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Funk GF. Continued alcohol use in patients with head and
neck cancer. Head Neck 2010;32:905–12
7 Mayne ST, Cartmel B, Kirsh V, Goodwin WJ Jr. Alcohol and
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alcohol drinking behaviors on treatment outcomes of patients
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9 Parker AJ, Marshall EJ, Ball DM. Diagnosis and management of
alcohol use disorders. BMJ 2008;336:496–501
10 Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C,
Paleri V et al. Prevalence of human papillomavirus in
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oropharyngeal and nonoropharyngeal head and neck cancer –
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region. Head Neck 2013;35:747–55
11 D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C,
Koch WM et al. Case-control study of human papilloma-
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1944–56
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follow-up of oral dysplasia – a systematic review and meta-ana-
lysis. Head Neck 2009;31:1600–9
13 Ho MW, Field EA, Field JK, Risk JM, Rajlawat BP, Rogers SN
et al. Outcomes of oral squamous cell carcinoma arising from
oral epithelial dysplasia: rationale for monitoring premalignant
oral lesions in a multidisciplinary clinic. Br J Oral Maxillofac
Surg 2013;51:594–9
14 Weller MD, Nankivell PC, McConkey C, Paleri V, Mehanna
HM. The risk and interval to malignancy of patients with laryn-
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lysis. Clin Otolaryngol 2010;35:364–72
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O, Axell T. A long-term follow-up study on the natural course of
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Pathol Med 2007;36:78–82
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et al. Screening programmes for the early detection and prevention
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affected Individuals and their Families. UK & Ireland Fanconi
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Address for correspondence:
Richard Shaw,
Department of Molecular and Clinical Cancer Medicine,
Institute of Translational Medicine,
University of Liverpool,
Aintree University Hospitals NHS Foundation Trust,
Liverpool, UK.
E-mail: Richard.shaw@liverpool.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S13–S22. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000372

Pre-treatment clinical assessment in head and neck

cancer: United Kingdom National Multidisciplinary
Guidelines

A ROBSON1, J STURMAN2, P WILLIAMSON3, P CONBOY4, S PENNEY5, H WOOD6

1
North Cumbria University Hospitals NHS Trust, Cumberland infirmary, Carlisle, 2Department of Anaesthesia,
Cumberland Infirmary, Carlisle, 3Department of ENT Surgery, St George’s Hospital NHS Trust, London,
4
Department of Otolaryngology-Head and Neck Surgery, University Hospitals of Leicester, Leicester Royal
Infirmary, Leicester, 5Department of Otolaryngology-Head and Neck Surgery, Manchester Royal Infirmary,
Manchester, and 6Department of Anaesthesia, Freeman Hospital, Newcastle upon Tyne NHS Foundation Trust,
Newcastle upon Tyne, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. This paper provides recommendations on the pre-treatment clinical assessment of patients
presenting with head and neck cancer.
Recommendations
• Comorbidity data should be collected as it is important in the analysis of survival, quality of life and functional
outcomes after treatment as well as for comparing results of different treatment regimens and different centres. (R)
• Patients with hypertension of over 180/110 or associated target organ damage, should have antihypertensive
medication started pre-operatively as per British Hypertension Society guidelines. (R)
• Rapidly correcting pre-operative hypertension with beta blockade appears to cause higher mortality due to stroke
and hypotension and should not be used. (R)
• Patients with poorly controlled or unstable ischaemic heart disease should be referred for cardiology assessment
pre-operatively. (G)
• Patients within one year of drug eluting stents should be discussed with the cardiologist who was responsible for
their percutaneous coronary intervention pre-operatively with regard to cessation of antiplatelet medication due to
risk of stent thrombosis. (G)
• Patients with multiple recent stents should be managed in a centre with access to interventional cardiology. (G)
• Surgery after myocardial infarction should be delayed if possible to reduce mortality risk. (R)
• Patients with critical aortic stenosis (AS) should be considered for pre-operative intervention. (G)
•Clopidogrel should be discontinued 7 days pre-operatively; warfarin should be discontinued 5 days
pre-operatively. (R)
• Patients with thromboembolic disease or artificial heart valves require heparin therapy to bridge peri-operative
warfarin cessation, this should start 2 days after last warfarin dose. (R)
• Cardiac drugs other than angotensin-converting enzyme inhibitors and angiotensin II antagonists should be
continued including on the day of surgery. (R)
• Angotensin-converting enzyme inhibitors and angiotensin II antagonists should be withheld on the day of
surgery unless they are for the treatment of heart failure. (R)
• Post-operative care in a critical care area should be considered for patients with heart failure or significant
diastolic dysfunction. (R)
• Patients with respiratory disease should have their peri-operative respiratory failure risk assessed and critical care
booked accordingly. (G)
• Patients with severe lung disease should be assessed for right heart disease pre-operatively. (G)
• Patients with pulmonary hypertension and right heart failure will be at extraordinarily high risk and should have
the need for surgery re-evaluated. (G)
• Perioperative glucose readings should be kept within 4–12 mmol/l. (R)
• Patients with a high HbA1C facing urgent surgery should have their diabetes management assessed by a diabetes
specialist. (G)
• Insulin-dependent diabetic patients must not omit insulin for more than one missed meal and will therefore
require an insulin replacement regime. (R)
• Patients taking more than 5 mg of prednisolone daily should have steroid replacement in the peri-operative
period. (R)
S14 A ROBSON, J STURMAN, P WILLIAMSON et al.

• Consider proton pump therapy for patients taking steroids in the peri-operative phase if they fit higher risk criteria. (R)
• Surgery within three months of stroke carries high risk of further stroke and should be delayed if possible. (R)
• Patients with rheumatoid arthritis should have flexion/extension views assessed by a senior radiologist
pre-operatively. (R)
• Patients at risk of post-operative cognitive dysfunction and delirium should be highlighted at pre-operative
assessment. (G)
• Patients with Parkinson’s disease (PD) must have enteral access so drugs can be given intra-operatively. Liaison
with a specialist in PD is essential. (R)
• Intravenous iron should be considered for anaemia in the urgent head and neck cancer patient. (G)
• Preoperative blood transfusion should be avoided where possible. (R)
• Where pre-operative transfusion is essential it should be completed 24–48 hours pre-operatively. (R)
• An accurate alcohol intake assessment should be completed for all patients. (G)
• Patients considered to have a high level of alcohol dependency should be considered for active in-patient withdrawal
at least 48 hours pre-operatively in liaison with relevant specialists. (R)
• Parenteral B vitamins should be given routinely on admission to alcohol-dependent patients. (R)
• Smoking cessation, commenced preferably six weeks before surgery, decreases the incidence of post-operative
complications. (R)
• Antibiotics are necessary for clean-contaminated head and neck surgery, but unnecessary for clean surgery. (R)
• Antibiotics should be administered up to 60 minutes before skin incision, as close to the time of incision as
possible. (R)
• Antibiotic regimes longer than 24 hours have no additional benefit in clean-contaminated head and neck
surgery. (R)
• Repeat intra-operative antibiotic dosing should be considered for longer surgeries or where there is major blood
loss. (R)
• Local antibiotic policies should be developed and adhered to due to local resistance patterns. (G)
• Individual assessment for venous thromboembolism (VTE) risk and bleeding risk should occur on admission
and be reassessed throughout the patients’ stay. (G)
• Mechanical prophylaxis for VTE is recommended for all patients with one or more risk factors for VTE. (R)
• Patients with additional risk factors of VTE and low bleeding risk should have low molecular weight heparin at
prophylactic dose or unfractionated heparin if they have severe renal impairment. (R)

Introduction status is not a reliable substitute for comorbidity

This section deals with the topics of patient assessment
and optimisation prior to treatment for head and neck
cancer (HNC). The importance of collaborative team-
work, structured pre-operative assessment, grading
and analysing comorbidity, and prophylaxis against
infection and venous thromboembolism (VTE) are
summarised in the section below.
Comorbidity: outcomes and data collection
The presence of illnesses unrelated to the tumour sig-
nificantly affects prognosis in HNC patients, and is
contributed to by tobacco, alcohol and substance
misuse. The Adult Comorbidity Evaluation 27 (ACE
27) and the Charlson Index are the most commonly
used indices to quantify comorbidity.
The National Cancer Intelligence Network (NCIN)
recommends that collection of an ACE 27 comorbidity
score be mandated for all adult cancer patients. This
facilitates surgical oncology research with the objective
of improving cancer care through improved patient
counselling and treatment planning. Information
should be extracted from notes rather than relying on
self-reporting.
Comorbidity scoring captures the impact of co-
existing diseases, but not the disease of interest.1,2
Performance status assesses the effect of all illnesses
on the patients’ functional ability. Performance
status as a prognostic measure, as they can each inde-
pendently lead to poor tolerance of treatment. There is
good evidence that integrating comorbidity with
staging systems produces better prognostic instru-
ments. The development of ‘prognostigrams’ relating
to tumour–node–metastasis (TNM) stage, comorbid-
ity and performance status require the accurate collec-
tion of these variables in large numbers as suggested
by NCIN.
The effects of increased pre-treatment comorbid
burden include:
• Adverse impact on short-term mortality of patients
with newly diagnosed head and neck squamous
cell carcinoma (HNSCC)
• Reduced overall survival in HNSCC and possible
predictor for distant metastases
• Adverse influence on disease-specific survival,
probably due to the advanced stage at presentation
and the likelihood of such patients undergoing less
aggressive treatment i.e. treatment selection
• Higher incidence of and more severe
complications
• Adverse impact on quality of life (QoL)
• Adverse impact on functional outcomes
• Increased cost of treatment.
PRE-TREATMENT CLINICAL ASSESSMENT IN HEAD AND NECK CANCER: UK GUIDELINES
The relationship between performance status and
survival is much less well-defined.
Recommendation
• Comorbidity data should be collected as it is
important in the analysis of survival, QoL and
functional outcomes after treatment as well as
for comparing results of different treatment
regimens and different centres. (R)
Pre-operative assessment
A good pre-operative assessment system will provide
an appropriately informed, consented and prepared
patient on the day of surgery, avoiding late cancellation
and preventable risk. It is imperative that referral for
pre-operative assessment takes place as early as pos-
sible within the patient pathway.
Measures of the effectiveness of a pre-operative assess-
ment service should be regularly audited. These include:
• Avoiding delay in listing and admission for
surgery
• Avoiding unnecessary or duplicate investigations
• High proportion of same day admissions for
surgery
• No cancellations as a result of inadequate investi-
gation or workup
• Length of hospital stay.
The role of the anaesthetist in pre-operative assess-
ment includes:
• Identification of the difficult airway
• Risk stratification and discussion
• Optimisation of comorbidities within the limited
timeframe prior to surgery
• Formulation of a plan for peri-operative care with
appropriate allocation to critical care resources.
Guidance for the use of pre-operative testing is avail-
able from National Institute for Health and Care
Excellence (NICE), The Clinical Audit and Practice
Advisory Group of ENT UK and the British
Association of Day Surgery and Royal College of
Anaesthetists.3,4 Individual department guidelines
should be developed, including the use of general
and dynamic testing.
There should be a clinical lead in each anaesthetic
department for pre-operative assessment and for head
and neck anaesthesia with established links to related
specialities.
Identification of the difficult airway
In head and neck practice, the surgeon and anaesthetist
have an important role in identifying the difficult
airway (Box I).
S15
BOX I
RISK FACTORS FOR A DIFFICULT INTUBATION
INCLUDE
• Previous difficult intubation
• Mallampati grade III or IV
• Thyromental distance <6 cm
• Reduced mouth opening, inter-dental distance
<3 cm
• Reduced neck extension
• Presence of retrognathia
• Poor dentition
• Obstructive laryngeal tumours
• Tongue base tumours
• Hypopharyngeal lesions
• Previous head and neck surgery or radiotherapy
A collaborative approach and communication greatly
reduces the risk associated with a difficult airway.
Suspected cases should be discussed between
surgeon and anaesthetist prior to the day of surgery
ideally with nasolaryngoscopy and scans to aid deci-
sion making. Airway assessment is imperfect in pre-
dicting problems and an airway strategy that
encompasses emergency options should be formulated
for both induction and the end of surgery. This strategy
must be communicated clearly to the entire team
working in theatre on the day and human factors
considered.
Risk stratification and optimisation of comorbidities
Assessment of risk. In recent years, there has been an
increasing focus on risk prediction in patients undergo-
ing major surgical procedures. In terms of risk stratifi-
cation, head and neck surgery is classed as
intermediate-risk surgery.
The POSSUM (Physiological and Operative
Severity Score for the Enumeration of Mortality and
Morbidity) score is a useful aid to predicting morbidity
but despite being a well-validated tool, it has not
demonstrated effective prediction of mortality in head
and neck surgery.
The extensively validated Revised (Lee) Cardiac
Risk Index (Box II) is a six point index score derived
from patients over the age of 49; it is used to assess
the risk of major cardiac event associated with non-
cardiac surgery. This and other scoring systems were
predominantly validated in the general and vascular
surgical populations, but evidence suggests that it is a
useful predictor of cardiovascular morbidity peri-
operatively in head and neck surgery, particularly
when combined with age over 70 as an additional
variable.
S16
BOX II
REVISED (LEE) CARDIAC RISK INDEX VARIABLES
• History of IHD
• History of congestive heart failure
• Cerebrovascular disease (stroke or transient
ischaemic attack)
• Diabetes requiring insulin use
• Chronic kidney disease (Creatinine > 2.0 mg/dl
or 177 μmol/l)
• High-risk surgery – intra-peritoneal, intra-
thoracic and suprainguinal vascular
Predicted risk of major cardiac event:
0 variables = 0.4 per cent risk
1 variable = 0.9 per cent risk
2 variables = 6.6 per cent risk
3 or more variables = 11 per cent risk
The assessment of dynamic function or aerobic fitness
is extremely important to aid quantification of risk and
allocation of critical care resources. Simple subjective
methods include the estimate of metabolic equivalents
(METs), where one MET equates to the oxygen con-
sumption of a 70 kg man at rest, four METs equate to
walking up one flight of stairs; failure to achieve this
is associated with increased risk. Dynamic testing of
functional capacity may include the use of shuttle
walk testing, 6 minutes walk testing, treadmill cardiac
testing and cardiopulmonary exercise testing (CPET).
CPET is currently the most reliable and objective
assessment of functional capacity; the anaerobic
threshold and peak oxygen consumption are proven
to be well correlated with morbidity and mortality in
the peri-operative period in major surgery; its applica-
tion to head and neck surgery is still being evaluated.
The following sections will concentrate on identifi-
cation of significant comorbidities and therapies
which require specific pre-operative management,
using a system-based approach.
Cardiovascular system. Between 40 and 50 per cent of
patients will have cardiovascular disease.5 All patients
over 55 years and those with diabetes or other cardiac
risk should have an electrocardiogram (ECG) as a
minimum pre-operative investigation.
Hypertension. Hypertension is the commonest cardio-
vascular comorbidity. There is evidence that hyperten-
sion with target organ damage is associated with a
small increased incidence of major cardiovascular events.
The diagnosis of hypertension should be made in
primary care. A patient with a blood pressure of
greater than 180/110 mm Hg has severe hypertension
and should not proceed to non-urgent surgery until
the blood pressure is controlled to below 160/100.
Patients with more moderate hypertension with asso-
ciated target organ damage are also at higher risk.
A ROBSON, J STURMAN, P WILLIAMSON et al.
Where surgery must proceed patients should be made
aware of the increased risk. Patients with hypertension
demonstrate a more labile haemodynamic response to
induction, airway instrumentation, surgical stimulus
and post-operative pain. The practice of rapidly correct-
ing pre-operative hypertension with beta blockade
appears to cause higher mortality due to stroke and
hypotension as per the PeriOperative ISchaemic
Evaluation (POISE) study.
Patients with hypertension pre-operatively should be
managed by their primary care doctor with introduction
of antihypertensive agents as per the British
Hypertension Society (BHS) guidelines.6
Ischaemic heart disease. Patients with poorly con-
trolled ischaemic heart disease (IHD) should be
referred for cardiology assessment. There is no evidence
that pre-operative percutaneous coronary intervention
(PCI) improves outcome, peri-operative nor long term,
in patients with stable coronary artery disease; however,
it is justifiable when it is likely to improve the patient’s
long-term prognosis, such as due to the presence of left
main stem stenosis, three-vessel disease or left ventricular
(LV) dysfunction. Referral to a cardiologist for patients
with recent unstable coronary symptoms should
precede surgery. If PCI is performed prior to major
surgery bare metal stents are preferred, as these require
only four to six weeks of dual antiplatelet therapy,
which otherwise markedly increases peri-operative
bleeding. Patients with poorly controlled IHD (including
recent myocardial infarction (MI)) or who have had
recent intervention should undergo surgery in a centre
with access to interventional cardiology.
Cardiac investigations. Echocardiography is indi-
cated in the situations shown in Box III.7
BOX III
INDICATIONS FOR ECHOCARDIOGRAM
• Documented IHD with reduced functional
capacity unexplained by other musculoskeletal
disease
• Dyspnoea without obvious non-cardiac cause
(e.g. METs < 4 or METs < 7 and dyspnoea with
normal PFTs)
• Murmur or history of murmur PLUS symptoms
suggestive of valve disease or abnormal ECG
• Known significant valve disease with change of
symptoms or no echo within two years
• New atrial fibrillation
• New left bundle branch block or left ventricular
hypertrophy on ECG
• Suspected cardiomyopathy
• Lung disease with suspicion of cardiac
involvement (cor pulmonale)
• Known or suspected pulmonary hypertension
PRE-TREATMENT CLINICAL ASSESSMENT IN HEAD AND NECK CANCER: UK GUIDELINES
Dobutamine stress echocardiography can provide a
useful dynamic assessment if IHD is suspected and
CPET is not possible. Patients with severe valvular
disease have an increased risk of surgery. Aortic sten-
osis can progress rapidly in the elderly population,
and those with critical aortic stenosis may need to be
considered for pre-operative intervention.
Arrhythmias and pacing. Atrial fibrillation and other
arrhythmias are frequently found at pre-operative
assessment; these may be known or new.
Management should focus on the rate control, appropri-
ate anticoagulation and identification of associated
risks such as structural heart disease or indication for
pre-operative pacing.
Cardiac pacemakers should have a recent battery and
threshold check within one year. Patients with implan-
table defibrillators require organisation with a cardi-
ology technician so that they can be deactivated in
the anaesthetic room and external pads placed; this is
due to the risk of inappropriate discharge due to anaes-
thetic drugs (suxamethonium) or movement. In both
cases, theatre alerts should be placed to remind staff
about diathermy risk and bipolar used.
Cardiac and anticoagulant drugs. Clopidogrel should
normally be discontinued 7 days pre-operatively;
aspirin should be continued without interruption.
Patients taking warfarin for uncomplicated atrial fibril-
lation can discontinue it 5 days pre-operatively, restart-
ing post-operatively when enteral function returns and
the risk of bleeding is low. Patients with thrombo-
embolic disease or artificial heart valves require
heparin therapy to bridge peri-operative warfarin cessa-
tion. This will normally be with therapeutic dose low
molecular weight heparin (LMWH) and can be
managed in the community either with self-injection
or district nurse involvement. Last dose should be 24
hours before the start of surgery. Patients with severe
renal impairment will require adjusted dosing or
occasionally unfractionated heparin infusion. LMWH
or heparin infusion will need to be continued post-
operatively until the INR is within the therapeutic
range.
Newer oral anticoagulants (e.g. Dabigatran and
Apixaban) have variable elimination times depending
on renal and liver function; these are non-reversible
agents and if there are no locally agreed policies,
advice should be sought from a haematologist.
There is increasing evidence that statin therapy
should be continued without interruption to prevent
peri-operative coronary syndromes due to its plaque
stabilising properties.
Provision should be made for enteral administration
of cardiac drugs as early as possible post-operatively,
and patients should continue the majority of these med-
icines up to admission. Angotensin-converting enzyme
(ACE) inhibitors and angiotensin II antagonists are a
source of debate; the majority of anaesthetists will
S17
choose to omit these drugs on the morning of
surgery, particularly if it is purely for hypertension
control.
Recommendations
• Patients with hypertension of >180/110 or
associated target organ damage, should have
antihypertensive medication started pre-
operatively as per BHS guidelines (R)
• Rapidly correcting pre-operative
hypertension with beta blockade appears to
cause higher mortality due to stroke and
hypotension and should not be used (R)
• Patients with poorly controlled or unstable
IHD should be referred for cardiology
assessment pre-operatively (G)
• Patients within one year of drug eluting stents
should be discussed with the cardiologist who
was responsible for their PCI pre-operatively
with regard to cessation of antiplatelet
medication due to risk of stent thrombosis (G)
• Patients with multiple recent stents should be
managed in a centre with access to
interventional cardiology (G)
• Surgery after MI should be delayed if possible
to reduce mortality risk (R)
• Patients with critical AS should be considered
for pre-operative intervention (G)
• Clopidogrel should be discontinued 7 days
pre-operatively; warfarin should be
discontinued 5 days pre-operatively (R)
• Patients with thromboembolic disease or
artificial heart valves require heparin therapy
to bridge peri-operative warfarin cessation; this
should start 2 days after last warfarin dose (R)
• Cardiac drugs other than ACE inhibitors and
angiotensin II antagonists should be
continued including on the day of surgery (R)
• Angotensin-converting enzyme inhibitors and
angiotensin II antagonists should be withheld
on the day of surgery unless they are for the
treatment of heart failure (R)
• Post-operative care in a critical care area
should be considered for patients with heart
failure or significant diastolic dysfunction (R)
Heart failure and diastolic dysfunction. Heart failure is
a considerably greater peri-operative risk factor than
angina or previous MI alone. New or poorly controlled
heart failure should be referred to cardiology for opti-
misation, with early commencement and uptitration
of an ACE inhibitor, unless contraindicated, whilst
that assessment is pending.
S18
Heart failure carries a 50 per cent four-year mortality
from diagnosis if the underlying cause cannot be
treated; 50 per cent of patients with severe heart
failure (symptomatic and frequent presentations) will
die within one year.
Post-operative care in a critical care area should be
considered for patients with heart failure or significant
diastolic dysfunction.
Right heart failure carries a very high peri-operative
risk, much more than LV failure, and there is little
available treatment. Right heart failure associated
with pulmonary hypertension carries extraordinary
risk and is discussed in the respiratory section.
Respiratory system. Significant respiratory disease
occurs in 20–30 per cent of patients and respiratory
morbidity is the most frequent medical complication
of major surgery and cause of intensive care unit
stay. Preoperative respiratory disease should be opti-
mised wherever possible and right heart disease and
pulmonary hypertension considered in those with sig-
nificant hypoxia (oxygen saturations <93 per cent) or
exercise limitation.
Respiratory investigations. Chest radiographs are not
required routinely from a fitness perspective; the func-
tional capacity of the patient is paramount here.
Cardiopulmonary exercise testing may be useful to
assess dynamic function and can demonstrate whether
respiratory disease is the main contributing factor to
generalised debility.
Intensive care must be planned for patients with sig-
nificant pulmonary hypertension.
Lung disease should be quantified with spirometry
and in severe cases arterial blood gas sampling. An
FEV1 of less than 25 per cent predicted poses a markedly
increased risk of post-operative ventilatory support, espe-
cially when accompanied by hypoxia, hypercarbia or cor
pulmonale. The risk of respiratory mortality alone may
outweigh any benefit from major surgery. The following
actions will optimise a patient’s condition for surgery:
• Optimise bronchodilator therapy
• Trial of steroid responsiveness in moderate and
severe disease
• Smoking cessation
• Peri-operative nebuliser therapy
• Treatment of inter-current chest infection, pos-
sibly delaying surgery
• Sputum sampling to enable ‘best guess’ treatment
of chest infection.
Patients with significant hypoxia (oxygen saturations
greater than 93 per cent) arterial blood gas estimation
should be performed to look for CO2 retention. Such
patients should be considered for an echocardiogram.
Obstructive sleep apnoea. It is useful to know the
degree of obstructive sleep apnoea (OSA) pre-operative-
ly to allow post-operative care planning and to consider
A ROBSON, J STURMAN, P WILLIAMSON et al.
the need to exclude pulmonary hypertension and right
heart failure, which may occur if there has been an
extended period of untreated OSA. Mask fitting
should be optimised and any change to anatomy that
could compromise use of the mask should be considered
and managed appropriately. Patients with proven or sus-
pected OSA and no continuous positive airway pressure
(e.g. not tolerated), will require critical care for at least
the first post-operative night.
Recommendations
• Patients with respiratory disease should have
their peri-operative respiratory failure risk
assessed and critical care booked
accordingly (G)
• Patients with severe lung disease should be
assessed for right heart disease pre-
operatively (G)
• Patients with pulmonary hypertension and
right heart failure will be at extraordinarily
high risk and should have the need for
surgery re-evaluated (G)
Endocrine system
Diabetes. Poor glycaemic control is associated with
increased wound infections, post-operative morbidity,
intensive care requirements and hospital mortality.
Peri-operative glucose readings should be kept within
the target range of 6–10 mmol/l or the acceptable
range of 4–12 mmol/l in order to reduce risk.
HbA1C is a useful indicator of diabetic control
within the preceding three months and patients with
an HbA1C greater than 69 should be considered as
higher risk of peri-operative poor glucose control. If
time allows, these patients should be referred to a dia-
betes specialist as important changes can be made to
glucose control within two to three weeks of surgery.
Clear and accessible peri-operative diabetes guide-
lines should be available in every hospital; National
Health Service (NHS) guidelines are available for the
management of adults with diabetes undergoing
surgery.8 Insulin-dependent diabetic patients must not
omit insulin for more than one missed meal and will
therefore require an insulin replacement regime, such
as a variable rate intra-venous insulin infusion
(VRIII) or a glucose potassium insulin infusion
(GKI) for major surgery. Many of the longer acting
insulins regimes should be continued at reduced dose
alongside the insulin replacement regime. Oral hypo-
glycaemic agents should be omitted on the day of
surgery and restarted when normal diet is resumed.
Many of these patients will also require a VRIII or
GKI. This can still be managed with day of surgery
admission in the well-controlled diabetic patient, pro-
vided that sufficient protocols are in place.
PRE-TREATMENT CLINICAL ASSESSMENT IN HEAD AND NECK CANCER: UK GUIDELINES
Many patients with HNC will have an adjusted diet post-
operatively and input from diabetic specialists is important
to successfully manage medication requirements.
Steroids. Steroid replacement is essential for those
with adrenal suppression from primary or secondary
causes to prevent potentially fatal adrenal crises; 60
per cent of patients taking 5 mg of prednisolone daily
fail a short Synacthen test and are therefore at risk of rela-
tive post-operative adrenal failure. Guidelines agreed
and awaiting publication by the AAGBI and agreed by
the Clinical Advisory Panel to the Addison’s Disease
Self-Help Group, recommend the use of peri-operative
steroid cover for all patients taking more than 5 mg pred-
nisolone daily, or the equivalent doses of hydrocorti-
sone 20 mg or dexamethasone 1 mg. Patients using
inhaled, intra-nasal or topical steroids may also be at
risk. Hydrocortisone is only therapeutic for 2–3 hours
after intra-venous bolus, so the more traditional QDS
bolusing can leave patients sub-therapeutic for several
hours before the next dose.
The recommended steroid replacement regime is as
follows: 100 mg IM hydrocortisone at induction fol-
lowed 4 hours later by 200 mg by intra-venous infusion
over 24 hours; this may be commenced intra-operatively.
This infusion should be continued until oral steroids can
be used. Oral dosing should be doubled for at least 48
hours for major surgery and then rapidly tapered back
to normal dosing. If intra-venous infusion is impossible,
a secondary option is IM 50 mg hydrocortisone QDS.
National Institute for Health and Care Excellence
guidelines regarding oral corticosteroids note a higher
risk of gastrointestinal bleeding and dyspepsia if
steroid use is associated with advanced cancer, older
age, concomitant non-steroidal anti-inflammatory med-
ications or anticoagulants, previous gastrointestinal
ulcer, bleed or perforation. These patients should be
considered for proton pump therapy.
Recommendations
• Peri-operative glucose readings should be
kept within 4–12 mmol/l (R)
• Patients with a high HbA1C facing urgent
surgery should have their diabetes
management assessed by a diabetes
specialist (G)
• Insulin-dependent diabetic patients must not
omit insulin for more than one missed meal
and will therefore require an insulin
replacement regime (R)
• Patients taking more than 5 mg of
prednisolone daily should have steroid
replacement in the peri-operative period (R)
• Consider proton pump therapy for patients
taking steroids in the peri-operative phase if
they fit higher risk criteria (R)
S19
Neurological system
Stroke. Peri-operative stroke occurs in approximately
1 in 1000 patients with no prior history of stroke. The
comparative odds ratios increase markedly in the pres-
ence of prior stroke.9
Where surgery cannot be delayed, attention must be
paid to cardiovascular stability with avoidance of sig-
nificant hypotension and head positioning to avoid
compression or distortion of the neck vessels, which
may impede cerebral perfusion pressure. Carotid dop-
plers are appropriate for stroke within 12 months.
Rheumatoid arthritis related neck instability. Patients
with rheumatoid arthritis are at risk of atlanto-axial sub-
luxation and subsequent cord injury and extreme caution
should be used at intubation and head positioning.10
There are no clear guidelines on the use of cervical
spine radiographs pre-operatively. Symptoms suggesting
a higher risk of atlanto-axial instability include hesitation
on neck movement, pain on movement radiating to the
occiput, paraesthesia to the shoulder blades on head
movement, or sensory loss in the hands. Up to 20 per
cent of patients with rheumatoid arthritis can demon-
strate abnormalities on radiographs and in view of the
movement often required at surgery for head and neck
disease it is advisable that these patients should have cer-
vical spine stability assessed radiologically. Flexion and
extension views of the cervical spine are required and
should be interpreted by a senior radiologist.
Recommendations
• Surgery within three months of stroke carries
high risk of further stroke and should be
delayed if possible (R)
• Patients with rheumatoid arthritis should
have flexion/extension views assessed by a
senior radiologist pre-operatively (R)
• Patients at risk of POCD and delirium should
be highlighted at pre-operative assessment (G)
• Patients with Parkinson’s disease (PD) must
have enteral access so drugs can be given
intra-operatively. Liaison with a specialist in
PD is essential (R)
Post-operative cognitive dysfunction (POCD) and post-
operative delirium. Post-operative cognitive dysfunction
is new cognitive impairment arising after a surgical
procedure, which may be permanent. The incidence
of POCD in non cardiac surgery is in the region of
20 per cent at one week and 10 per cent at three
months, rising with age. The incidence of delirium
(temporary acute confusional state) is higher.
Every effort should be made to highlight these risk
factors at pre-operative assessment so the anaesthetic
and post-operative care can be tailored accordingly
(Box IV). This may include the use of short acting
S20
anaesthetic agents, close monitoring for infection and
ensuring adequate pain relief; but also includes ensuring
the patient has all necessary aids such as for hearing and
sight.
BOX IV
RISK FACTORS FOR POCD OR DELIRIUM INCLUDE
• Age > 70
• Preoperative cognitive impairment or dementia
• Depression
• Preoperative alcohol misuse
• Visual impairment
• Renal dysfunction
• Tobacco use
• Previous delirium
Haematological system. The commonest haematological
abnormality is anaemia, usually due to iron deficiency.
It is essential that haematinic evaluation is completed to
look for the specific deficiency, which may be asso-
ciated with nutritional failure. A source of iron defi-
ciency anaemia should be always sought (occult
malignancy, ulcer disease).
Treatment should be based on the active replacement
of the haematinics, whether B12, folate or iron. Iron
replacement can be oral or intravenous; oral therapy
will only be effective if absorption is likely and there
is at least six weeks before surgery. Intravenous iron is
increasingly used and can cause a meaningful rise in
haemoglobin levels within two to three weeks.
Erythropoietin should be considered on advice from a
haematologist or nephrologist for patients with
anaemia due to renal disease or anaemia related to
chronic disease.
Recommendations
• Intravenous iron should be considered for
anaemia in the urgent HNC patient (G)
• Preoperative blood transfusion should be
avoided where possible (R)
• Where pre-operative transfusion is essential it
should be completed 24–48 hours pre-
operatively (R)
Preoperative transfusion should be avoided wherever
possible and considered on a case by case basis rather
than a target haemoglobin level. There is no evidence
to support a cut off transfusion point and there is signifi-
cant risk independently associated with peri-operative
blood transfusion. Where pre-operative transfusion
cannot be avoided, it should be completed at least
24–48 hours pre-operatively in order to allow time for
regeneration of 2,3-diphosphoglycerate in stored red
A ROBSON, J STURMAN, P WILLIAMSON et al.
cells, which ensures optimum oxygen delivery by the
haemoglobin.
Alcohol and smoking
Alcohol misuse. There is an increased rate of high
alcohol intake in patients with HNCs. General post-
operative complication rates are approximately 50 per
cent higher for patients who drink 5–6 units of
alcohol per day compared with those who drink 0–3
units. If untreated, 6 per cent of alcohol-dependent
patients will develop clinically relevant symptoms of
withdrawal, and up to 10 per cent of these will experi-
ence delirium tremens. Acute alcohol withdrawal in the
context of major surgery can cause significant morbid-
ity and a peri-operative mortality of up to 10 per cent.
An accurate alcohol assessment should include
details of intake and level of dependency as well as
impact on general health. Alcohol withdrawal should
be considered in any patient who has hazardous drink-
ing levels defined as more than 5 units per day for men,
3 units per day for women. Information about appropri-
ate alcohol counselling and support should be provided
to patients considered at risk.
Identification of alcohol dependency at pre-operative
assessment enables further investigation for associated
conditions. It also allows planning for pre-operative
detoxification, prophylactic intervention, and a higher
level of vigilance during admission for the early signs
of alcohol withdrawal.
Patients considered to have a high level of depend-
ency should be considered for active in-patient with-
drawal at least 48 hours pre-operatively in liaison
with relevant specialists.
Thiamine deficiency is common in patients with
alcohol dependency and oral absorption can be poor.
Parenteral B vitamins (Pabrinex) should be used
before surgery to prevent Wernicke–Korsakoff syn-
drome in those patients with high levels of alcohol
intake.
Tobacco use. Smoking tobacco before diagnosis in
patients with HNC has a negative correlation with sur-
vival. A significant proportion of patients attending
cancer diagnostic clinics are smokers. Continued
tobacco use in the period leading up to surgery is asso-
ciated with higher morbidity and mortality in general.
Smokers have a considerably increased risk of both
intra-operative and post-operative complications,
including a 3 to 6-fold increase of peri-operative pul-
monary complications. Patients requiring flap recon-
structions have higher flap failure rates and greater
wound infection rates. Continued smoking during
radiotherapy treatment increases complications in
patients with laryngopharyngeal cancer and increases
the risk of treatment failure. Smoking shortens overall
survival and increases both the risk of recurrence and
of developing a second primary tumour.
Ideally patients should be supported to stop smoking
from the time of their initial clinic visit. Stopping for
PRE-TREATMENT CLINICAL ASSESSMENT IN HEAD AND NECK CANCER: UK GUIDELINES
24–48 hours pre-operatively normalises the amount of
carbon monoxide in the blood, which may be as high as
15 per cent in smokers, allowing better oxygen carrying
capacity of the blood to the heart and surgical wounds.
Stopping for four to six weeks will allow the immune
system recovery. Stopping for six to eight weeks
allows recovery of respiratory tract cilia function.
Nicotine withdrawal should be treated both pre- and
post-operatively.
The UK Government has set up a comprehensive
NHS Stop Smoking Service and a range of
products and interventions are available. Many trusts
now use the successful Stop Before Your Op
campaign.
Recommendations
• An accurate alcohol intake assessment should
be completed for all patients (G)
• Patients considered to have a high level of
alcohol dependency should be considered for
active in-patient withdrawal at least 48 hours
pre-operatively in liaison with relevant
specialists (R)
• Parenteral B vitamins should be given
routinely on admission to alcohol-dependent
patients (R)
• Smoking cessation, commenced preferably six
weeks before surgery, decreases the incidence
of post-operative complications (R)
Nutritional failure
Nutritional failure impacts negatively on mortality,
infection and wound healing. Detailed nutritional
assessment and support should be instituted pre-opera-
tively for all patients facing major head and neck
surgery as a matter of routine. Dietician-led nutritional
support intervention should be provided to any at-risk
patients as part of their multidisciplinary management.
Antibiotic prophylaxis
The rationale for considering surgical antibiotic
prophylaxis is based on reducing major morbidity,
reducing patient length of stay, reducing hospital
costs and decreasing overall consumption of antibio-
tics. Antibiotic use is not without risk and careful
adherence to local antibiotic policies is essential to
account for local resistance patterns.
Risk factors affecting the incidence of surgical site
infection can be both patient and operation associated.
Head and neck cancer patients who smoke, are obese
(over 20 per cent of ideal body weight), diabetic and
immunosuppressed, and have advanced disease or
require free flap reconstruction have the greatest risk
of surgical wound infection. Operative factors include
duration of surgery, antimicrobial prophylaxis and sur-
gical technique (haemostasis, appropriate use of drains,
S21
tissue handling and wound closure). The risks of infec-
tion can be minimised by:
• Day of surgery admission where possible
• Advising patients to shower or bathe on the day
before or the day of surgery
• Methycillin-resistant Staphylococcus aureus
screening and use of topical agents to reduce car-
riage if required
• Use of antibiotic prophylaxis, where indicated
• Aseptic surgical technique and careful tissue
handling
• Minimising post-operative stay.
The Scottish Intercollegiate Guidelines Network has
published a review of the role of antibiotic prophylaxis
in surgery, updated in April 2014. Whilst the guidelines
are for surgery in general, the search criteria and con-
clusions include evidence and specific conclusions
for head and neck surgery. It must be remembered
that antibiotic use is not without risk and reducing
inappropriate prescribing is one of the aims of rationa-
lising surgical antibiotic prophylaxis.
In the setting of clean head and neck surgery for
benign disease, antibiotic prophylaxis is not recom-
mended. For surgery with malignant disease that is
clean (e.g. neck dissection) antibiotic prophylaxis can
be considered. For contaminated and clean-contami-
nated surgery antibiotic prophylaxis is recommended.
In this setting, a single dose of antibiotic with a long
enough half-life to achieve activity throughout the
operation is recommended. The duration of prophylac-
tic antibiotics should not be more than 24 hours. The
choice of antibiotic should ensure broad-spectrum
cover for aerobic and anaerobic organisms.
Recommendations
• Antibiotics are necessary for clean-
contaminated head and neck surgery, but
unnecessary for clean surgery (R)
• Antibiotics should be administered up to 60
minutes before skin incision, as close to the
time of incision as possible (R)
• Antibiotic regimes longer than 24 hours have
no additional benefit in clean-contaminated
head and neck surgery (R)
• Repeat intra-operative antibiotic dosing
should be considered for longer surgeries or
where there is major blood loss (R)
• Local antibiotic policies should be developed
and adhered to due to local resistance
patterns (G)
The timing of the administration of prophylactic anti-
biotics is important. Intravenous antibiotic should be
given up to 60 minutes before the skin is incised.
S22
There is some evidence which suggests this dose
should be as close to incision as possible. Repeat
dosing should be considered when the operation is sig-
nificantly longer than the half-life of the antibiotic
given. In the event of major intra-operative blood loss
(>1500 ml), additional prophylactic antibiotic dosage
should be considered after fluid replacement to main-
tain serum concentrations.
Thromboembolic disease prophylaxis
The stated incidence of clinically significant venous
thromboembolism (VTE) varies from 0 to 13 per cent
in HNC operations.11 Variation may relate to extent
of surgery, and non-pharmacological mechanical inter-
ventions, with most series showing an incidence of less
than 1 per cent. Early mobilisation and adequate hydra-
tion status are essential therapeutic interventions.
Current NICE guidance on VTE and Scottish
Intercollegiate Guidelines Network guidelines cover
all surgical patients without specific reference to head
and neck cases. Individual assessment for risk of
VTE and bleeding should occur on admission and be
repeated at least every 48 hours throughout admission.
All patients with one or more of the risk factors
(Box V) should receive mechanical prophylaxis from
admission (anti-embolism stockings to knee or thigh,
or foot impulse devices or intermittent pneumatic com-
pression devices) unless contraindicated. Do not offer
anti-embolism stockings to patients with cardiac
failure, peripheral arterial disease or neuropathy or
local tissue damage. Patients should be encouraged to
mobilise and remain well hydrated.
BOX V
RISK FACTORS FOR VENOUS
THROMBOEMBOLISM INCLUDE
Advancing age >60 years
Obesity – BMI > 30 kg/m2
Varicose veins
Family history of VTE
Thrombophilias
Presence of cancer or other thrombotic states
Significant medical comorbidities including
heart disease
Oestrogen containing drugs including hormone
replacement therapy or tamoxifen
Immobility
Anaesthetic and surgical time >90 minutes
If the surgical procedure is associated with a low risk of
major bleeding and taking into account individual risk
factors, prophylactic LMWH, or unfractionated heparin
for those with severe renal impairment, may be added
until mobility is restored. From the risk factors detailed
above it can be seen that the majority of head and neck
patients are likely to be appropriate for combined
pharmacological and mechanical prophylaxis regimes.
A ROBSON, J STURMAN, P WILLIAMSON et al.
Recommendations
• Individual assessment for VTE risk and
bleeding risk should occur on admission and
be reassessed throughout the patient’s stay (G)
• Mechanical prophylaxis for VTE is
recommended for all patients with one or
more risk factors for VTE (R)
• Patients with additional risk factors of VTE
and low bleeding risk should have LMWH at
prophylactic dose or unfractionated heparin if
they have severe renal impairment (R)
References
1 Wang JR, Habbous S, Epsin-Garcia O, Chen D, Huang SH,
Simpson C et al. Co-Morbidity and performance status as inde-
pendent prognostic factors in head and neck squamous cell car-
cinoma patients. Head Neck 2014. doi: 10. 1002/hed.23947.
2 Paleri V, Wight RG, Silver CE, Haigentz M Jr, Takes RP, Bradley
PJ et al. Comorbidity in head and neck cancer: a critical appraisal
and recommendations for practice. Oral Oncol 2010;46:712–19
3 The Association of Anaesthetists of Great Britain and Ireland.
AAGBI safety guideline. Pre-operative assessment and patient
preparation. The role of the anaesthetist. 2010. https://www.
aagbi.org/sites/default/files/preop2010.pdf (accessed 15
October 2015)
4 Kristensen SD, Knuuti J, Saraste A, Anker S, Bøtker HE, Hert SD
et al. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardio-
vascular assessment and management: The Joint Task Force on
non-cardiac surgery: cardiovascular assessment and management
of the European Society of Cardiology (ESC) and the European
Society of Anaesthesiology (ESA). Eur Heart J 2014;35:2383–431
5 Datema FR, Poldermans D, Baatenburg de Jong RJ. Incidence
and prediction of major cardiovascular complications in head
and neck surgery. Head Neck 2010;32:1485–93
6 Association of Anaesthetists of Great Britain and Ireland &
British Hypertensive Society. Pre-operative measurement of
adult blood pressure and management of hypertension. Draft
guidelines May 2015. http://www.aagbi.org/sites/default/
files/Pre-operative%20hypertension%20guideline%2020150429.
pdf (accessed 1 November 2015)
7 Clinical indications for echocardiography. British Society of
Echocardiography 2011. http://www.bsecho.org/indications-
for-echocardiography/ (accessed 1 November 2015)
8 NHS diabetes guideline: Management of adults with diabetes
undergoing surgery and elective procedures: improving standards.
2011. http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_
Surgery_Adults_Full.pdf (accessed 5 November 2015)
9 Jørgensen ME, Torp-Pedersen C, Gislason GH, Jensen PF,
Berger SM, Christiansen CB et al. Time elapsed after ischemic
stroke and risk of adverse cardiovascular events and mortality
following elective noncardiac surgery. JAMA 2014;312:269–77
10 Fombon FN, Thompson JP. Anaesthesia for adult patients with
rheumatoid arthritis. CEACCP 2006;6:235–9
11 Gavriel H, Thompson E, Kleid S, Chan S, Sizeland A. Safety of
thromboprophylaxis after oncologic head and neck surgery.
Study of 1018 patients. Head Neck 2013;35:1410–14
Address for correspondence:
Andrew Robson,
Department of Otolaryngology,
North Cumbria University Hospitals NHS Trust,
Cumberland Infirmary,
Carlisle, UK
E-mail: Andrew.Robson@ncuh.nhs.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S23–S27. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000384

Anaesthesia for head and neck surgery: United

Kingdom National Multidisciplinary Guidelines

P CHARTERS1, I AHMAD2, A PATEL3, S RUSSELL4

1
Department of Anaesthesia, University Hospital Aintree, Liverpool, 2Department of Anaesthesia, Guy’s and St
Thomas’ NHS Foundation Trust, London, 3Department of Anaesthesia, Royal National Throat Nose & Ear
Hospital, London, and 4Department of Anaesthesia, Queen Elizabeth Hospital, Birmingham NHS Foundation
Trust, Birmingham, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. The anaesthetic considerations for head and neck cancer surgery are especially challenging
given the high burden of concurrent comorbidity in this patient group and the need to share the airway with the
surgical team. This paper provides recommendations on the anaesthetic considerations during surgery for head
and neck cancer.

Recommendations
• All theatre staff should participate in the World Health Organization checklist process. (R)
• Post-operative airway management should be guided by local protocols. (R)
• Patients admitted to post-operative care units with tracheal tubes in place should be monitored with continuous
capnography. Removal for tracheal tubes is the responsibility of the anaesthetist. (R)
• Anaesthetists should formally hand over care to an appropriately trained practitioner in the post-operative or
intensive care unit. (G)
• Intensive care unit staff looking after post-operative tracheostomies must be clear about which patients are not
suitable for bag-mask ventilation and/or oral intubation in the event of emergencies. (R)

Introduction the implications of post-operative result and how the

The anaesthetic and surgical team need to have a clear
understanding about their respective roles in managing
the ‘shared airway’. This will vary with the surgery
and the anaesthetist’s requirement to avoid airway com-
promise by way of gas exchange or soiling. A guaranteed
airway from pre-operative ward care through to safe dis-
charge must be considered as an essential duty of care for
any institution undertaking surgery of this nature.
Pre-operative assessment
Comorbidity and pre-operative assessment are consid-
ered elsewhere in the guidelines.1 Because of the
‘superficial’ nature of head and neck surgery, patients
are less likely to be considered ‘unfit’ relative to
those presenting for body cavity cancer surgery. One
must be aware that this group of patients are prone to
sepsis and multi-organ failure needing intensive care
support. Such issues should be anticipated and dis-
cussed with the patient and relatives as part of the
consent for surgery. Similarly, because many of the
patients are elderly and with limited support at home,
patient will be able to cope should be part of the deci-
sion to offer surgical treatment.
General anaesthetic considerations
World Health Organization (WHO) checklist
All theatre staff are recommended to participate in this
initiative to ensure that teams work effectively and that
the right patients get the right surgical procedure they
have consented to. In addition, reference should be
made to anticipated airway problems and ensuring the
necessary equipment is available.2,3
Monitoring requirements
The basic requirements for monitoring maintenance of
anaesthesia and recovery are outlined in the
Association of Anaesthetists of Great Britain and
Ireland recommendations (4th edition, 2007) and
advanced monitoring is usually only considered for
long procedures or when excessive blood loss is a rea-
sonable possibility.4
S24
Prophylaxis for thromboembolism is discussed
elsewhere in these guidelines1
Airway considerations
While patients presenting for head and neck surgery
may have co-existent problems that could make
airway management difficult (e.g. receding jaw,
restricted neck movement, etc.), it is usually the size
and site of tumour that causes concern. Any instrumen-
tation needs to be judicious, including use of airway
aids, in order that any problems with visualisation
and/or airway soiling are not dramatically worsened.
Patients with pharyngolaryngeal tumours frequently
have residual food debris at laryngoscopy which may
interfere with the view obtained especially for instru-
ments with a limited field of vision. Contractures
resulting from the previous treatment are common in
patients with head and neck cancer. They may have
obvious external deformities and restricted movements
(e.g. limited neck extension). Rigidity and distortion of
the oropharyngeal tissues can interfere with facemask
ventilation and conventional laryngoscopy.
Oxygenation
Maintenance of oxygenation is fundamental to airway
management and techniques that extend the apnoeic
window allow more controlled, less hurried and more
careful, gentle instrumentation. This may reduce the
deterioration in the airway following instrumentation
and the subsequent difficulty in facemask ventilation
which can lead to a ‘cannot intubate, cannot ventilate’
scenario.5 Traditional methods of increasing the
apnoeic window involve spontaneous facemask venti-
lation with 100 per cent oxygen. Trans-nasal high-
flow rapid insufflation ventilatory exchange or
THRIVE delivered through a nasal high-flow oxygen
delivery system has recently been shown to increase
the apnoea time in head and neck patients including
those with stridor to an average of 17 minutes. Trans-
nasal high-flow rapid insufflation ventilatory exchange
combines apnoeic oxygenation, continuous positive
airway pressure and flow-dependent deadspace flush-
ing and has the potential to change the nature of diffi-
cult intubations from a hurried stop–start process to a
more controlled event, with an extended apnoeic
window and reduced iatrogenic trauma.6
Induction of anaesthesia
If a patient is already at risk of airway obstruction
due to tumour bulk, then it is probable that they will
be at greater risk following induction of anaesthesia,
whether intravenous or inhalational. Even local anaes-
thesia is not without risk because severe airway
obstruction precipitated by laryngospasm has occurred.
In some institutions, ventilation is established prior to
induction of general anaesthesia via temporary crico-
P CHARTERS, I AHMAD, A PATEL et al.
thyroid or trans-tracheal access. (The latter is obviously
preferable in patients with subglottic extension of a
laryngeal tumour.) The use of muscle relaxant drugs
to facilitate laryngoscopy in these cases is controversial
because even if intubation conditions are improved this
may be at the cost of greater risk of airway obstruction.
Current practice has also been influenced by the intro-
duction of many new intubation devices, very few of
which have been reported in large series of head and
neck cancer patients.
Fluid management and blood loss
Many resections and free tissue transfers will not be
associated with significant bleeding, though this is
not necessarily true for tongue and mandibular resec-
tions where brisk bleeding may occur. Hypotensive
conditions may minimise blood loss and haemodilution
is practiced in some institutions with a view to
improved blood flow in free flaps. Intra-operative
haemoglobin and central venous pressure measure-
ments help in monitoring the need for blood transfu-
sion. Cardiac monitoring was used regularly in only 9
per cent of UK units in an audit in 2012.7
Length of operative procedure
For lengthy operative procedures increased attention
needs to be paid to the inevitable consequences of pro-
longed immobility, impaired homeostasis (associated
with general anaesthesia) and the saturation of fatty
tissue with anaesthetic agents. These equate to the
need to protect from gravity-related pressure effects,
thermal homeostasis, retention of urine and prolonged
wake up time.
Post-operative airway management
Currently there is widely diverse practice in terms of
post-operative airway management of head and neck
cancer patients. For example, at one end of the spec-
trum almost all free-flap reconstructions are managed
with temporary tracheostomy whereas elsewhere, over-
night ventilation followed by extubation the following
morning is the expected norm. There are differences
as to which patients warrant this level of airway protec-
tion and even as to suitability for delivery of such care
by immediate return to the ward vs high dependency or
intensive care. The need for advanced airway protec-
tion is to avoid airway obstruction due to haemorrhage
or other surgical complication affecting the airway.
Tracheostomy is an intervention with its own risks
including inadvertent decannulation and is also asso-
ciated with increased hospital stay. Overnight intub-
ation may carry increased risk for patients with
significant comorbidity. The relative decrease in
senior and junior intensive care unit staff with no
airway training may also condition local perceptions
of relative risk.
ANAESTHESIA FOR HEAD AND NECK SURGERY: UK GUIDELINES
Recommendations
• All theatre staff should participate in the
WHO checklist process (R)
• Post-operative airway management should be
guided by local protocols (R)
Specific operative considerations
The compromised airway
In the patient who presents with acute airway com-
promise the obvious option is to consider a tracheos-
tomy under local anaesthesia. Even this may not be
an easy option in the patient who is already desaturated,
uncooperative and unable to lie flat. Because of the
need to attend to the problem, there will be limited
time for radiological imaging. Heliox mixtures may
provide symptomatic relief, while further information
is obtained, e.g. nasendoscopy to assess the airway
objectively. Many of these cases will prove to have a
laryngeal tumour, in which case surgeons generally
prefer that tracheostomy is avoided. It may be possible
to de-bulk the tumour once intubation is achieved, but
experienced practitioners need to be involved if this is
to be attempted.
Tumour de-bulking to improve airway patency
Whether or not the patient presents as an emergency,
there are two objectives. Firstly a biopsy will be
taken for tissue diagnosis and secondly the tumour
bulk will be reduced so as to minimise any likelihood
of obstruction. Immediately after the procedure, the
anaesthetist needs to confirm that the airway will be
unobstructed (e.g. from a remaining tissue fragment
acting as a ball-valve) and satisfactory from the point
of view of bleeding.
Formal tumour assessment for treatment planning
(examination under anesthesia and biopsy)
This is the more usual situation where the risk of airway
obstruction is considered less likely. The anaesthetist
will usually have information about the lesion (e.g.
photograph or clinical diagram) under consideration
and ideally, shared visualisation of the lesion prior to
induction.
Tubeless anaesthesia
Ideally, any surgeon would wish to have an unrestricted
view of the lesion to be operated on. In the case of
laryngeal tumours, the most common compromise is
to use a small diameter micro-laryngoscopy tube
(6.0 mm ID or smaller). Other alternatives which
allow a much less restricted field are: very narrow
tubes used with gas exchanged by jet ventilation, a
crico-thyroid airway (again usually with jet ventila-
tion), ad hoc arrangements for repeated tube insertion
S25
and removal, and total intravenous anaesthesia with
spontaneous respiration (usually also with local anaes-
thesia applied to the vocal cords). These alternatives
tend to become more of a problem if the operative pro-
cedure is prolonged.
Laser surgery
The risk of airway fires due to laser is low provided
careful precautions including laser safe tubes are
used. Post-operative haemorrhage and oedema risks
mean that tracheostomy remains an important consider-
ation in extensive resections.
Free flaps
Attempts have been made to increase the success of
free-flap anastomoses by medical means but there
is no general consensus as to what if anything is
efficacious. Doppler probes are available to monitor
anastomotic vessel patency but are expensive and
tend to be restricted in use to inaccessible sites, com-
posite flaps (where skin colour may not reflect the
deeper layer viability), continued arterial spasm risk
and patients who have had previous radiation. Early
return to theatre, however, in the event of compromise,
may allow the flap to be salvaged if the blood flow can
be restored.
Management of surgical complications
Neck haematoma, flap failures, fistulas and airway man-
agement issues (e.g. re-establishment of a closed trache-
ostomy) are common reasons for a return to theatre.
When patients are admitted to a post-anaesthesia care
unit with tracheal tubes in place, continuous capnogra-
phy monitoring is appropriate and their removal
remains the anaesthetist’s responsibility.8 It is import-
ant to be aware of the current state of the airway
anatomy relative to the previous surgery and the time
for healing. Severe bleeding is possible if major neck
vessels are eroded. This sort of haemorrhage can
arise suddenly and with little warning. Everyone
involved needs to be acutely aware of what is needed
by way of immediate measures (e.g. pressing on the
neck in the event of a ‘carotid blowout’ or removing
the skin clips in the event of a rapid expanding haema-
toma) vs the need to get to the theatre to attend to the
problem directly. Proximity to the emergency theatres
and kit available on the ward should be important
considerations.
Recommendation
• Patients admitted to post-operative care units
with tracheal tubes in place should be
monitored with continuous capnography.
Removal for tracheal tubes is the
responsibility of the anaesthetist (R)
S26
Recovery from anaesthesia
Emergence from anaesthesia phenomena
Commonly seen problems include transient hyperten-
sion, disorientation and/or agitation and shivering.
Analgesic requirements tend to be less than for body
cavity surgery, but this will not necessarily be the
case in patients on moderate doses of opiates for pre-
operative pain problems. Flap donor sites may have
their own analgesic requirements.
Immediate return to theatre from recovery
The most likely indications are bleeding and/or airway
obstruction. The need for a covering tracheostomy may
have been underestimated. Airway oedema can develop
rapidly and is often precipitated by venous obstruction,
posture change (e.g. allowing patients to lie down flat
immediately prior to ward transfer) and Valsalva man-
oeuvres. Neck haematomas can be particularly decep-
tive because any associated airway oedema bears
little resemblance to the apparent severity of neck swel-
ling. If there is time it may be helpful to perform nasen-
doscopy prior to deciding how to anaesthetise for
corrective surgical measures.
High dependency and intensive care
Many head and neck surgery patients will be looked
after in enhanced care by virtue of their comorbidity,
the length of surgical procedure or the need to
closely monitor the free flap. It is unusual for any
patient to be ventilated post-operatively. Standardised
handover forms are commonly used to summarise
surgery and anaesthesia intra-operative events with a
description of the resulting airway anatomical configur-
ation and advisory options in the event of potential
airway problems.
Care of the tracheostomy
The Intensive Care Society has produced guidelines for
the management of tracheostomy (and temporary
tracheostomy in particular).9 Percutaneous and surgical
tracheostomy is commonly used to help manage lower
airway and aspiration problems in the general intensive
care setting. Anticipated complications include bleed-
ing, tube obstruction and accidental decannulation.
Dealing with any of these issues commonly requires
senior and experienced staff and they will frequently
resort to conventional oral intubation to secure the
airway prior to re-establishing the compromised trache-
ostomy, but oral intubation may not be feasible either
because this is physically impossible (e.g. the post-
laryngectomy patient) or because oral intubation would
seriously jeopardise the surgical result (e.g. immediately
after partial laryngectomy or major tongue resection).
These situations can be very serious both because of the
technical challenges posed and the limited time available
for re-establishing the compromised airway. It is essential
that anyone dealing with these situations must know what
P CHARTERS, I AHMAD, A PATEL et al.
surgery has been performed and whether oral intubation
is a feasible alternative.
Enhanced recovery programmes (ERP) for head and
neck cancer patients
An ERP can be formulated around the head and neck
cancer patient’s overall journey.10,11 Stratified intro-
duction of interventions with simple early objectives
may yield a positive impact on outcomes. These pro-
grammes have been shown to improve outcomes in
patients undergoing major colorectal and gynaeco-
logical procedures, by reducing length of stay and 30-
day morbidity. Extrapolation of these concepts to
patients with head and neck cancer undergoing major
resections and free-flap surgery may help in improving
outcomes. Relevant pre-operative measures might
include carbohydrate loading with carbohydrate
drinks 1–2 days before surgery. Intra-operative goals
include: directed fluid therapy using cardiac output
monitoring to optimise fluid management; mainten-
ance of normothermia and tight glycaemic control. In
the post-operative phase, early enteral feeding is
advocated.
Recommendations
• Anaesthetists should formally hand over care
to an appropriately trained practitioner in the
post-operative or intensive care unit (G)
• Intensive care unit staff looking after post-
operative tracheostomies must be clear about
which patients are not suitable for bag-mask
ventilation and/or oral intubation in the event
of emergencies (R)
Key points
• The main difference between anaesthesia for major
head and neck surgery and that for body cavity
cancer is that because it is relatively superficial
patients with greater comorbidity can be treated
• Overall care of the airway for these patients should
be seen as an institutional responsibility where all
the weakest points in care delivery are addressed
• Perioperative assessment should be comprehensive
enough to make all airway issues predictable and
suitably planned for
• Pre-oxygenation by trans-nasal high-flow rapid
insufflation ventilator exchange (“Thrive”) signifi-
cantly extends the window for tracheal intubation,
making it less stressful and less traumatic
• Operatively “shared airway” working (between the
surgeon and anaesthetist) should be seamless with
anticipation of one another’s requirements
• Post-operative airway issues can occur even with
minor surgical procedures, again these should be
anticipated and planned for
ANAESTHESIA FOR HEAD AND NECK SURGERY: UK GUIDELINES
• Significant diversity exists in the expected post-
operative care for major cases (mainly tracheostomy
versus overnight intubation and extubation the fol-
lowing day)
• Staff caring for patients with tracheostomy and
serious airway pathology must be aware of the
special risks this implies, suitably trained and
aware of the relevant guidelines
• Urgent airway issues need a planned response that
takes into account local resource allocation and prox-
imity between wards, theatre and HDU/ICU
• When urgent airway issues arise the institution must
be able to match the response to the problem with
appropriate seniority of expertise.
References
1 Robson A, Sturman J, Williamson P, Conboy P, Penney S,
Wood H. Pre-treatment clinical assessment in head and neck
cancer: United Kingdom National Multidisciplinary
Guidelines. J Laryngol Otol 2016;130(Suppl S2):S13–22
2 World Alliance for Patient Safety. WHO Surgical Safety
Checklist and Implementation Manual Geneva. Switzerland:
WHO Press, World Health Organization, 2008
3 Haynes AB, Weiser TG, Berry WR, Lipsitz SR, Breizat AH,
Dellinger EP et al. A surgical safety checklist to reduce morbid-
ity and mortality in a global population. N Engl J Med 2009;360:
491–99
4 Birks RJS, Gemmell LW, O’Sullivan EP, Rowbotham DJ,
Sneyd JR. Recommendations for Standards of Monitoring
During Anaesthesia and Recovery. London: The Association
of Anaesthetists of Great Britain and Ireland, 2007
S27
5 Cook TM, Woodall N, Frerk C. Major Complications of Airway
Management in the United Kingdom. London: The Royal
College of Anaesthetists, 2011
6 Patel A, Nouraei SA. Transnasal humidified rapid-insufflation
ventilatory exchange (THRIVE): a physiological method of
increasing apnoea time in patients with difficult airways.
Anaesthesia 2015;70:323–29
7 Chalmers A, Turner MW, Anand R, Puxeddu R, Brennan PA.
Cardiac output monitoring to guide fluid replacement in
head and neck microvascular free flap surgery – what is
current practice in the UK? Br J Oral Maxillofac Surg 2012;
50:500–3
8 Whitaker DK, Booth H, Clyburn P, Harrop-Griffiths W, Hosie
H, Kilvington B et al. Immediate post-anaesthesia recovery
2013: association of anaesthetists of Great Britain and Ireland.
Anaesthesia 2013;68:288–97
9 Bodenham A, Bell D, Bonner S, Branch F, Dawson D, Morgan P
et al. Standards for the Care of Adult Patients with a Temporary
Tracheostomy: Standards and Guidelines. Intensive Care Society,
2014. http://www.ics.ac.uk/EasysiteWeb/getresource.axd?Ass
etID=2212&type=full& servicetype=Attachment (accessed
4th March 2016)
10 Khoo CK, Vickery CJ, Forsyth N, Vinall NS, Eyre-Brook IA. A
prospective randomized controlled trial of multimodal peri-
operative management protocol in patients undergoing elective
colorectal resection for cancer. Ann Surg 2007;245:867–72
11 Walter CJ, Collin J, Dumville JC, Drew PJ, Monson JR.
Enhanced recovery in colorectal resections: a systematic
review and meta-analysis. Colorectal Dis 2009;11:344–53
Address for correspondence:
Peter Charters,
Department of Anaesthesia,
University Hospital Aintree,
Liverpool, UK
E-mail: pete.charters@btinternet.com
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S28–S31. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000396

Imaging in head and neck cancer: United Kingdom

National Multidisciplinary Guidelines

H LEWIS-JONES1, S COLLEY2, D GIBSON3

1
Department of Radiology, University Hospital Aintree, Liverpool, 2Department of Radiology, University Hospital
Birmingham NHS Trust, Birmingham, UK, and 3Fiona Stanley Hospital, Murdoch, Perth, WA, Australia

Abstract
This guideline is endorsed by the specialty associations involved in the care of head and neck cancer patients in the
UK. This paper summarises the current imaging modalities in use for head and neck cancer evaluation. It highlights
their role in the management with recommendations on modality choice for each cancer subsite.
Recommendations
• Offer appropriate radiological imaging, based on tumour extent, site and local expertise, to stage tumours and
plan treatment for patients diagnosed with head and neck cancer. (G)
• Consider positron emission tomography combined with computed tomography (PET–CT) imaging if
conventional cross-sectional imaging identifies no primary site. (R)
• Offer PET–CT imaging 12 weeks after non-surgical treatment to detect residual disease. (R)

Introduction Imaging modalities

Imaging in head and neck cancer has developed
enormously over the last few decades. Advanced
cross-sectional imaging modalities allow accurate
staging of disease and contribute significantly to man-
agement decisions and prognosis. As a core member of
a multidisciplinary team, the radiologist has a key role
in presenting relevant multi-modality findings that
define disease extent, help with surveillance and high-
light pertinent co-morbidities.1 This approach also aids
pre-treatment counselling and patient consent.
Prior to imaging, the primary site and the presence
or absence of neck metastases of a head and neck
cancer has often been established clinically and it is
not unusual for a histological diagnosis to have been
secured from a representative biopsy. Therefore, the
primary role of radiology is in accurately staging
the full extent and distant spread of disease with the
current tumour–node–metastasis (TNM) system, with
an emphasis on features that will influence surgical or
non-surgical treatment options.
The areas that radiological assessment should focus
on are:
• Local extent of the primary tumour
• Spread to locoregional cervical lymph nodes
• Detection of metastatic disease precluding cure
and synchronous primary tumours of the lung
and upper aero-digestive tract.
Computed tomography (CT)
Contrast-enhanced CT is the mainstay for imaging
primary disease. It is widely available and established
in practice. It incurs a significant radiation penalty
and iodinated contrast medium is contraindicated in
those with severe renal impairment. Conventionally,
centres would image the neck and chest at presentation
from the skull base to below the diaphragm.
Spatially good but at a radiation cost, CT provides
limited soft tissue resolution. Bone detail such as
with mandibular or skull base involvement is a major
strength. Modern multislice, slip-ring CT detector tech-
nology rapidly acquires images without movement
artefact as potential head and neck cancer patients
may have difficulty with breathing, swallowing secre-
tions and lying flat. Multiplanar and volume rendered
images are easily reconstructed. Contrast-enhanced
CT allows opacification of vascular structures whilst
tumours generally tend to be slower to enhance with
a reduced wash out.
Magnetic resonance imaging (MRI)
Magnetic resonance imaging reflects biochemical
tissue characteristics and is largely influenced by
proton density and other in situ paramagnetic sub-
stances such as blood products and melanin content.
Alongside the permanent bore magnet, additional
IMAGING IN HEAD AND NECK CANCER: UK GUIDELINES
transient magnetic gradients allow the development of
an ever increasing array of sequences that are able to
reflect pathological processes from normal surrounding
tissues. Multiple manufacturers may have differing
terms for sometimes similar sequence parameters.
T1-weighted ‘anatomical’ images have excellent
spatial resolution, whilst T2-weighted images preferen-
tially highlight oedema and therefore pathology. A
short tau inversion-recovery (STIR) sequence retains
the positive attributes of a T2-weighted image and sup-
presses surrounding fat signal in normal or invaded
tissues to best depict abnormal tissue as a bright,
high signal. Magnetic resonance imaging has the
ability to dramatically improve tissue contrast reso-
lution when compared with CT and, in compliant
patients without contraindications, it is the imaging
modality of choice for defining the primary extent of
oral and oropharyngeal cancers. Detrimentally, when
compared with CT, scan times are much longer and
can vary from about 2–10 minutes for each sequence,
during which the patient must keep relatively still.
Intravenous gadolinium contrast agents allow static
and dynamic vascular assessments of a tumour and,
when combined with fat suppression techniques, this
can increase the conspicuity of occult pathology.
Dental amalgam can reduce the image quality both
for CT and MR imaging that makes interpretation
more challenging.
Positron emission tomography combined with CT
(PET–CT)
Positron emission tomography combined with CT
whole-body imaging uses various labelled tracers to
fuse conventional, anatomical CT images with a func-
tional ‘map’ of the disease process. This is conducted
on a single gantry at a single appointment. The com-
monest tracer is 18 fluoro-deoxyglucose, which is pref-
erentially transported and trapped into hypermetabolic
cancerous or inflamed tissues. It is detected with a
gamma camera array. The patient’s fasted baseline
glucose level should be measured and the isotope is
injected intravenously approximately 1 hour before
imaging. The patient refrains from talking or chewing.
Actual image acquisition takes about 30–45 minutes.
Modern scanner design accurately co-registers
metabolic tissue activity with its precise anatomical
location.
In 2013, the Royal College of Radiologists published
evidence-based guidelines for PET–CT use in head
and neck cancer. Evaluating the patient with malignant
cervical adenopathy from an unknown primary is one
of the main, up-front indications. Positron emission
tomography will detect an occult primary in approxi-
mately one third of cases. Positron emission tomog-
raphy combined with CT is also valuable in the
assessment of suspected recurrence of head and neck
cancer when there are extensive, confounding post-
treatment changes on conventional imaging modalities.
S29
Its added benefit in routine surveillance following treat-
ment is still being assessed. Along with other modal-
ities, it has a role in staging malignant thyroid disease
including medullary thyroid carcinoma.
Ultrasound
Offered as part of a modern one-stop service, ultra-
sound, alongside fine needle aspiration cytology,
allows rapid imaging assessments for those with an
undiagnosed neck lump or suspected metastatic
disease in the neck. This technique can be notoriously
operator dependent, but has no detrimental patient
effects. Following slide preparation, best cytological
practice recommends prompt adequacy assessments
and, ideally, the cytologist should be onsite for diag-
nostic advice. In reality, a shortage of radiology and
histopathological input makes such universal service
developments difficult.
Ultrasonography comfortably delineates thyroid
pathology and can detect occult pathological nodes
(necrosis, microcalcification, etc.) that may feel clinic-
ally normal in size. A normal node should remain ovoid
in shape with a short axis diameter less than 10 mm
with a preserved echogenic hilum. Retropharyngeal
and superior mediastinal nodes cannot be assessed
with this modality.
Current doctrine dictates that clinically and radio-
logically N0 disease from high-risk primary sites is
presumed to have small volume nodal micrometastasis
that routinely requires prophylactic first-line treatment
as no available tests can guarantee a true pathological
N0 status.
Fluoroscopy
There are a variety of scenarios when contrast swallows
and fluoroscopy are used in head and neck cancer,
although the availability of local expertise can be vari-
able. Contrast swallows can be used to assess the length
of a malignant proximal oesophageal stricture, while
the risk of airway aspiration or penetration is dynamic-
ally assessed by videofluoroscopy. Alternative, non-
oncological causes for dysphagia such as a pharyngeal
pouch may be diagnosed. Water soluble contrast
studies are advised when the risk of aspiration is
high, for instance, following recurrent chest infections
or diminished pharyngeal sensory/motor function
after surgery or radiation. The integrity of a surgical
anastomosis or the tract of an entero-cutaneous fistula
can also be well evaluated. These studies are often
jointly performed with a speech and language therapist
to facilitate decision making and may improve func-
tional outcomes.
Chest imaging
With common aetiological factors, patients with head
and neck cancer have higher incidences of synchronous
and metachronous primary lung tumours that may be
S30
disseminated at presentation. At staging, CT imaging of
the thorax is routinely advised.
The most common protocol for patients with a head
and neck cancer will therefore be to image the primary
site by either contrast-enhanced CT or magnetic reson-
ance imaging (MRI), perform CT imaging of the chest
and PET–CT for the unknown primaries.
Specific tumour sites
This section deals with specific tumour sites and high-
lights areas where radiological evaluation is particular-
ly important and often difficult.
Oral cavity
Preferred imaging modality: MRI
Tongue tumours are routinely evaluated with MRI to
aid treatment choices and prognosis. Early or advanced
cancers of the buccal mucosa, retromolar trigone, palatal
and floor of mouth are more difficult to evaluate reliably
by imaging alone and good clinical correlation is essen-
tial. Perineural and marrow involvement is best defined
at MRI.
In an attempt to avoid osteoradionecrosis, orthopan-
tomograms are still requested to proactively treat dental
caries and peri-apical disease.
Oropharynx
Preferred imaging modality: MRI
Small or subclinical primaries in the tonsil and
tongue base that often present with cervical lymph-
adenopathy can be difficult to identify with all forms
of imaging including PET–CT. These tumours are
often best evaluated at MRI with STIR sequences and
often, may only be localised retrospectively after exam-
ination and biopsy under anaesthesia. Extension of
mucosal tumours into the adjacent structures and
neck spaces is well depicted with MR imaging.
Nasopharynx
Preferred imaging modality: MRI
Nasopharyngeal tumours commonly present at an
advanced stage with palpable nodal neck disease.
Magnetic resonance imaging allows accurate classifica-
tion of the primary site and nodal disease as per the
TNM classification, based on disease extent.
Hypopharynx
Preferred imaging modality: MRI
In those patients who have difficulty with swallow-
ing, aspiration or breathing when supine, a CT scan
will need to be strongly considered.
Larynx
Preferred imaging modality: MRI
Disease at the level of the vocal cords presents
early with dysphonia and is well localised. Imaging is
H LEWIS-JONES, S COLLEY, D GIBSON
often unnecessary for T1 disease unless extralaryngeal
disease, cartilage involvement, nodal metastasis or
chest pathology is suspected. MRI with contrast is the
gold standard for depiction of cartilage involvement.
Recommendations
• Offer appropriate radiological imaging, based
on tumour extent, site and local expertise, to
stage tumours and plan treatment for patients
diagnosed with head and neck cancer (G)
• Consider PET–CT imaging if conventional
cross-sectional imaging identifies no primary
site (R)
• Offer PET–CT imaging 12 weeks after
non-surgical treatment to detect residual
disease (R)
Salivary glands
Malignant salivary glands neoplasms are a very
heterogenous group of tumours, where tumour behav-
iour and prognosis is dictated by the histology.
Ultrasound techniques have a significant role to play
in assessing the parenchymal mass, local adenopathy
and guiding biopsies. Perineural or skull base involve-
ment often requires a combined multi-modality CT
and MR approach. The best imaging modality may
be guided by site-specific characteristics such as
respiratory motion artefact.
Sinuses
MRI with contrast is the modality of choice to assess
surgical resectability issues around intracranial and
orbital disease spread. Skull base involvement usually
requires a complementary CT study.
Post-operative imaging
The choice of imaging in the post-operative scenario is
determined by the specific clinical question posed.
Complications are frequent with difficult head and
neck resections. When the specific question is over
potential residual or recurrent disease, following
either surgery or chemoradiotherapy, the choice for
baseline imaging mainly falls between a contrast CT
of the neck and chest and a timely PET–CT study.
As an exception, MRI has a large role to play specific-
ally for nasopharyngeal, sinonasal and skull base
tumour follow up.2 Early detection of residual disease
is vital to planning further curative attempts. The
timing of the scan is important. Dedicated CT gives
better resolution and anatomical detail at the primary
site as well as detecting subcentrimetre early metastatic
disease in the lungs. Obliteration of fat planes and ana-
tomical distortions makes interpretation difficult. A
negative, normal PET–CT 12 weeks post-treatment
likely offers the best prognostic reassurance currently.3
PET–CT fails to reliably distinguish inflammatory
IMAGING IN HEAD AND NECK CANCER: UK GUIDELINES
elements from malignant foci. Ultrasound guided pro-
cedures still have a role to play in sampling in-
determinate, persistent enlarged cervical nodes.
Key points
• Accurate image interpretation and staging heavily
influences optimal treatment strategies
• Contrast-enhanced computed tomography of the
skull base, neck and chest is ubiquitous in nature,
readily available and the workhorse for routine
tumour–node–metastasis staging of head and neck
cancers
• Positron emission tomography combined with com-
puted tomography is of proven diagnostic benefit
when searching for the unknown primaries, when
conventional imaging is non-informative
• In compatible patients, magnetic resonance imaging
has superior soft tissue characterisation at several
primary sites including oropharynx, nasopharynx/
skull base and sinuses that greatly aid surgical plan-
ning and resections
S31
• Ultrasound image guided diagnostic fine needle and
core biopsies are well established and cost-effective
in the context of good cytological/histological support
• In certain instances, multi-modality approaches are
complementary to each other but should not adverse-
ly impact on the speed of the diagnostic pathway.
References
1 Olliff J, Richards P, Connor S, Wong WL, Beale T, Madani G.
Head and neck cancers. In: Nicholson T, ed. Recommendations
for Cross-Sectional Imaging in Cancer Management, 2nd edn.
London: The Royal College of Radiologists, 2014. pp 3–19
2 Hermans R, ed. Head and Neck Cancer Imaging. New York:
Springer, 2012
3 Mehanna H, Wong WL, McConkey CC, Rahman J, Robinson M,
Hartley A et al. PETCT Surveillance versus Neck Dissection in
Advanced Head and Neck Cancer, N Engl J Med 2016;374:
1444–54
Address for correspondence:
Daren Gibson,
Fiona Stanley Hospital,
Murdoch, Perth, WA, Australia
E-mail: gibsondaren9@googlemail.com
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S32–S40. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000402

Nutritional management in head and neck cancer:

United Kingdom National Multidisciplinary
Guidelines

B TALWAR1, R DONNELLY2, R SKELLY3, M DONALDSON4

1
Head and Neck Centre, University College London Hospital NHS Foundation Trust, London, 2Department of
Nutrition and Dietetics, Guy’s and St Thomas’ NHS Foundation Trust, London, 3Department of Nutrition and
Dietetics, Aintree University Hospitals NHS Foundation Trust, Liverpool, and 4Department of Dietetics and
Nutrition, QMC Campus, Nottingham University Hospitals NHS Trust, Nottingham, UK

Abstract
Nutritional support and intervention is an integral component of head and neck cancer management. Patients can be
malnourished at presentation, and the majority of patients undergoing treatment for head and neck cancer will need
nutritional support. This paper summarises aspects of nutritional considerations for this patient group and provides
recommendations for the practising clinician.
Recommendations
• A specialist dietitian should be part of the multidisciplinary team for treating head and neck cancer patients
throughout the continuum of care as frequent dietetic contact has been shown to have enhanced outcomes. (R)
• Patients with head and neck cancer should be nutritionally screened using a validated screening tool at
diagnosis and then repeated at intervals through each stage of treatment. (R)
• Patients at high risk should be referred to the dietitian for early intervention. (R)
• Offer treatment for malnutrition and appropriate nutrition support without delay given the adverse impact on
clinical, patient reported and financial outcomes. (R)
• Use a validated nutrition assessment tool (e.g. scored Patient Generated–Subjective Global Assessment or
Subjective Global Assessment) to assess nutritional status. (R)
• Offer pre-treatment assessment prior to any treatment as intervention aims to improve, maintain or reduce
decline in nutritional status of head and neck cancer patients who have malnutrition or are at risk of
malnutrition. (G)
• Patients identified as well-nourished at baseline but whose treatment may impact on their future nutritional
status should receive dietetic assessment and intervention at any stage of the pathway. (G)
• Aim for energy intakes of at least 30 kcal/kg/day. As energy requirements may be elevated post-operatively,
monitor weight and adjust intake as required. (R)
• Aim for energy and protein intakes of at least 30 kcal/kg/day and 1.2 g protein/kg/day in patients receiving
radiotherapy or chemoradiotherapy. Patients should have their weight and nutritional intake monitored
regularly to determine whether their energy requirements are being met. (R)
• Perform nutritional assessment of cancer patients frequently. (G)
• Initiate nutritional intervention early when deficits are detected. (G)
• Integrate measures to modulate cancer cachexia changes into the nutritional management. (G)
• Start nutritional therapy if undernutrition already exists or if it is anticipated that the patient will be unable to eat
for more than 7 days. Enteral nutrition should also be started if an inadequate food intake (60 per cent of
estimated energy expenditure) is anticipated for more than 10 days. (R)
• Use standard polymeric feed. (G)
• Consider gastrostomy insertion if long-term tube feeding is necessary (greater than four weeks). (R)
• Monitor nutritional parameters regularly throughout the patient’s cancer journey. (G)
• Pre-operative:
○ Patients with severe nutritional risk should receive nutrition support for 10–14 days prior to major surgery
even if surgery has to be delayed. (R)
○ Consider carbohydrate loading in patients undergoing head and neck surgery. (R)
• Post-operative:
○ Initiate tube feeding within 24 hours of surgery. (R)
○ Consider early oral feeding after primary laryngectomy. (R)
NUTRITIONAL CONSIDERATIONS IN HEAD AND NECK CANCER: UK GUIDELINES S33

• Chyle Leak:
○ Confirm chyle leak by analysis of drainage fluid for triglycerides and chylomicrons. (R)
○ Commence nutritional intervention with fat free or medium chain triglyceride nutritional supplements either
orally or via a feeding tube. (R)
○ Consider parenteral nutrition in severe cases when drainage volume is consistently high. (G)
• Weekly dietetic intervention is offered for all patients undergoing radiotherapy treatment to prevent weight loss,
increase intake and reduce treatments interruptions. (R)
• Offer prophylactic tube feeding as part of locally agreed guidelines, where oral nutrition is inadequate. (R)
• Offer nutritional intervention (dietary counselling and/or supplements) for up to three months after treatment. (R)
• Patients who have completed their rehabilitation and are disease free should be offered healthy eating advice as
part of a health and wellbeing clinic. (G)
• Quality of life parameters including nutritional and swallowing, should be measured at diagnosis and at regular
intervals post-treatment. (G)

Introduction
Nutrition and Dietetic services should be organised to
provide a seamless service at any stage of the patient
pathway. There should be access to dedicated, site-spe-
cific dietitians for high-quality service delivery and
contribution as a core member of the head and neck
multidisciplinary team.1 Early identification of high-
risk patients and intervention with nutrition support
should be included as part of the planning for every
patient when treatment options are being considered.1,2
This should include quality of life (QoL) issues to
address psychosocial, rehabilitation and survivorship
needs of patients and carers.
Recommendation
• A specialist dietitian should be part of the
multidisciplinary team for treating head
and neck cancer patients throughout the
continuum of care as frequent dietetic
contact has been shown to have enhanced
outcomes (R)
Recommendations
• Patients with head and neck cancer should be
nutritionally screened using a validated
screening tool at diagnosis and then repeated at
intervals through each stage of treatment (R)
• Patients at high risk should be referred to the
dietitian for early intervention (R)
Impact of malnutrition
Patients with head and neck cancer are at risk of malnu-
trition as a result of the site of their cancer, the disease
process and the treatment. Patients may have long
standing dietary habits and detrimental lifestyle
factors such as alcohol misuse that may predispose
them to malnutrition. Regardless of presenting body
mass index (BMI), unintentional weight loss of 10 per
cent or greater in the preceding six months may lead
to a range of problems3 as highlighted in Box I.4

BOX I
MALNUTRITION ASSOCIATED MORBIDITY
Nutritional screening
The purpose of nutritional screening is to identify • Increased risk of infection
patients who are malnourished or at risk of becoming • Delayed wound healing
malnourished as early as possible.1,2 All inpatients on
• Impaired function of cardiac and respiratory
admission and all outpatients should be screened to
systems
identify those who require early nutritional intervention
and prompt referral.1,2 Table I shows the various • Muscle weakness
screening tools available. • Depression
• Poor QoL
Monitoring • Increased risk of post-operative complications
Screening should be repeated weekly for inpatients. For • Reduced response to chemotherapy and
outpatients, weight should be recorded at each out- radiotherapy
patient visit and weight loss of 2 kg or more within a • Increased mortality rate
two-week period reported to the dietitian.1,2
S34 B TALWAR, R DONNELLY, R SKELLY et al.

TABLE I Cancer cachexia

NUTRITIONAL SCREENING AND ASSESSMENT TOOLS Cachexia syndrome results in decreased appetite, weight
loss, metabolic alterations and an inflammatory state that
Screening tool Information Validated in
cancer cannot be fully reversed by conventional nutritional
patients support and leads to progressive functional impairment.
Pro-inflammatory processes can lead to insulin resist-
The Subjective Global Assesses nutritional Yes
Assessment (SGA) status based on ance, increased loss of body fat, muscle mass and
tool features of the production of acute phase proteins. Cytokine-induced
history and physical metabolic alterations can prevent cachectic patients
examination
The patient generated An adaptation of the Yes from regaining body cell mass during nutritional
– Subjective Global SGA tool for support, and are not relieved by conventional nutritional
Assessment (PG- assessing the intervention. Attempts to modulate these changes by
SGA) nutritional status and
is patient generated other means should be integrated into the management
The Malnutrition Compares favourably Yes of cancer patients. As a minimal goal body weight
Screening Tool with the PG-SGA should be maintained and further loss prevented. The
The Malnutrition Currently used by many No
Universal Trusts across the UK management approach should be multifactorial and
Screening Tool to screen patients includes assessment and ongoing monitoring with inten-
sive nutritional support, anti-inflammatory treatment,
symptom control as well as oncological treatment
Early nutritional intervention is essential to correct pre- options to reduce the catabolic effect of the cancer.6
existing nutritional deficiencies with regular reviews
throughout the patient’s journey in order to optimise
nutritional status and correct nutrition-related problems Estimating nutritional requirements
at each stage of treatment.1,5 Cancer itself does not have a consistent effect on
resting energy expenditure, but may be influenced by
oncological treatment. Resting energy expenditure
Recommendation can be unchanged, increased, or decreased.2 Cancer
patients are mildly hypermetabolic with an excess
• Offer treatment for malnutrition and energy expenditure of between 138 and 289 kcal/
appropriate nutrition support without delay day. Total energy expenditure and protein requirements
given the adverse impact on clinical, patient for non-obese ambulatory patients using their actual
reported and financial outcomes (R) body weight can be estimated as follows:
Energy, 30–35 kcal/kg/day and protein, 1.2 g/kg/
day.1 These may be less accurate for severely malnour-
ished, morbidly obese and surgical patients.
Nutritional assessment
Following nutritional screening a full nutritional
assessment should be undertaken in a pre-treatment
assessment clinic setting and at regular intervals
Recommendations
during a patient’s treatment trajectory1,2 (Table II). • Aim for energy intakes of at least 30 kcal/kg/
day. As energy requirements may be elevated
post-operatively, monitor weight and adjust
Recommendations intake as required (R)
• Use a validated nutrition assessment tool (e.g. • Aim for energy and protein intakes of at least
scored Patient Generated–Subjective Global 30 kcal/kg/day and 1.2 g protein/kg/day in
Assessment or Subjective Global Assessment) patients receiving radiotherapy or
to assess nutritional status (R) chemoradiotherapy
• Offer pre-treatment assessment prior to any • Patients should have their weight and
treatment as intervention aims to improve, nutritional intake monitored regularly to
maintain or reduce decline in nutritional status determine whether their energy requirements
of head and neck cancer patients who have are being met (R)
malnutrition or are at risk of malnutrition (G)
• Patients identified as well-nourished at
baseline but whose treatment may impact on
their future nutritional status should receive Refeeding syndrome
dietetic assessment and intervention at any Refeeding is a syndrome consisting of metabolic dis-
stage of the pathway (G) turbances that occur as a result of reintroduction of
nutrition to patients who are starved or severely
NUTRITIONAL CONSIDERATIONS IN HEAD AND NECK CANCER: UK GUIDELINES S35

TABLE II
NUTRITIONAL ASSESSMENT PARAMETERS
Clinical observation

• Ability to chew and swallow

• Clinical signs of weight loss e.g. ill-fitting dentures/clothing
• Medical history which may affect nutritional intake e.g. coeliac disease, diabetes

Dietary history Review of recent intake (24 hours recall), with attention being paid to:

• Fluid intake
• Changes in texture
• Reports of fullness
• Length of time and effort taken to eat
• Changes in appetite
• Gastrointestinal function

Calculation of Energy:
requirements
• 25–35 kcal/kg/day dependant on activity level. Can increase further if major complications.

Protein:

• 0.8–2.0 g/kg/day for depleted of treatment complications

Fluid:

• 30–35 ml/kg/day increases in infection and excessive fluid losses

Vitamins and minerals:

• As per recommended daily amounts unless considered deficient

Proposed treatment

• Disease status, tumour site

• Nutritional implications of previous and current treatment plan

Anthropometry

• Height
• Weight
• Weight history
• Percentage weight change
• Body mass index; <18.5 kg/m2 suggests undernutrition
• Triceps skinfold thickness indicates fat stores
• Mid arm muscle circumference indicates lean tissue mass
• Hand grip strength assesses muscle function

Biochemistry

• Urea and electrolytes – indicate fluid status although can be disrupted by disease state and treatment
• Albumin – not good indicator of nutritional status due to its long half-life (17–20 days) and it is affected by
stress and sepsis
• Pre-albumin – shorter half-life 2–3 days but also affected by infection and stress
• C-reactive protein – indication of acute phase response
• Transferrin – affected by inflammation and infection
• Total lymphocyte count – affected by infection
• Refeeding syndrome risk

Social information

• Alcohol intake
• Smoking
• Substance misuse
• Social support
• Dentition
• Access to food and cooking skills
• Social and financial circumstances
• Time taken to eat and drink
• Patient perception of nutritional status
S36 B TALWAR, R DONNELLY, R SKELLY et al.

malnourished. It can occur irrespective of the feeding

route. The main feature is hypophosphataemia but can
feature abnormal sodium and fluid balance; changes in
glucose, protein, and fat metabolism, thiamine defi-
ciency, hypokalaemia and hypomagnesaemia.7
The nationwide incidence of refeeding syndrome in
head and neck cancer is unknown. By defining refeed-
ing syndrome as a reduction in serum phosphate to
below 0.4 mmol/l,1,7 retrospective data from a regional
cancer centre found 37.5 per cent of patients to be at
risk as defined by National Institute for Health and
Care Excellence criteria (see Box II) with an incidence
rate of 9.5 per cent. A suggested management plan for
refeeding syndrome is shown in Figure 1.

Recommendations
• Perform nutritional assessment of cancer
patients frequently (G)
• Initiate nutritional intervention early when
deficits are detected (G)
FIG. 1
• Integrate measures to modulate cancer Management of re-feeding syndrome (reproduced with permission
cachexia changes into nutritional from Mehanna et al.7).
management (G)

• Reduce the adverse effects of anti-tumour therapies,

BOX II
CRITERIA FOR DETERMINING PEOPLE AT
MODERATE OR HIGH RISK OF DEVELOPING
REFEEDING SYNDROME2
• Prevent and treat undernutrition.
Nutritional support should be considered in the fol-
lowing scenarios:

Patient has one or more of the following:
• Body mass index less than 16 kg/m2
• Unintentional weight loss greater than 15 per
cent within last three to six months
• Little or no nutritional intake for more than 10
days
• Low levels of potassium, phosphate, or
magnesium prior to feeding
Or patient has two or more of the following:
• Body mass index less than 18.5 kg/m2
• Unintentional weight loss greater than 10 per
cent within last three to six months
• Little or no nutritional intake for more than
5 days
• A history of alcohol abuse or drugs, including
insulin, chemotherapy, antacids or diuretics
Nutrition support
The aims of nutrition support are to:
• Improve the subjective QoL
• Enhance anti-tumour treatment effects
• Body mass index <18.5 kg/m2
• Unintentional weight loss >10 per cent over three to
six months
• A BMI <20 kg/m2 and unintentional weight loss
over three to six months
• Minimal intake >5 days
• Increased nutritional requirements due to catabolism.
Types of nutrition support
Nutritional intervention should be tailored to meet the
needs of the patient and be realistic for the patient to
achieve. There are three main methods of nutrition
support: oral, enteral and parenteral. Parenteral nutri-
tion support is rarely used in the head and neck
setting. It should however be considered if required.
Oral nutrition support
Nutritional interventions include relaxation of previous
therapeutic diets to minimise further nutritional com-
promise and to positively influence QoL outcomes.8
Food fortification is first line advice; however, this
may not necessarily be appropriate due to the side
effects and intensity of treatment regimens. Patients
may require more intensive nutritional support
methods from the beginning of treatment over and
above traditional food fortification methods with the
NUTRITIONAL CONSIDERATIONS IN HEAD AND NECK CANCER: UK GUIDELINES
early use of oral nutrition support, e.g. nutritionally
complete liquid supplements. This can be initiated at
any point from diagnosis. There are a variety of oral
nutritional support products available. The choice
will depend on patient preference, current macro
and micro nutrient intake and local policy.
Enteral nutrition (EN) support
The choice of feeding route will depend upon local
arrangements, however clinical considerations should
include: site of tumour, treatment plan and intent, pre-
dicted duration of enteral feeding and patient choice.9,10
The types of tubes available are nasogastric, nasojejunal,
tracheo – oesophageal fistulae tubes, orogastric, gastros-
tomy, gastro-jejunostomy and jejunostomy. Nasogastric,
nasojejunal, oro gastric, trachea – oesophageal fistulae
tubes are all recommended for short-term use (less than
four weeks). National Institute for Health and Care
Excellence guidelines on enteral feeding suggest that if
enteral feeding is expected to be required for longer
than four weeks then gastrostomy insertion is
recommended.2
Consideration should be made with regard to the
timing and method of gastrostomy placement.
Screening and assessment for suitability and method
of gastrostomy insertion by endoscopic, radiological
or surgical approach is essential. Assessment of co-
morbidities and contraindications should be undertaken
in order to prevent complications of tube insertion prior
to oncological treatment. Variation exists for the pre-
ferred method of insertion and is dependent on local
policy. There are no nationally agreed selection criteria
for gastrostomy placement in head and neck patients.
Comparison between studies is difficult and made
more challenging by limitations in study design as
well as the inability to stratify data meaningfully into
groups with adequate patient numbers by similar treat-
ment modality, type of gastrostomy and timing of tube
placement.9,10 Evidence-based practice guidelines,
based on a systematic review of literature across the
entire nutrition care pathway, following a National
Health and Medical Research Council’s process for
assessing the level of evidence and evaluating the
body of literature, have been published.1 Although the
optimal method of tube feeding remains unclear,10,11
it is widely accepted that prophylactic tube feeding
compared with reactive tube feeding or oral intake
alone improves nutritional outcomes with reduced
weight loss, and can therefore contribute towards clin-
ical, financial and QoL aspects.1,12 However, high-
level evidence base is yet to be generated to confirm
the benefits.13,14 Appropriate decision making around
prophylactic tube feeding must consider all factors
that impact on nutrition including patient demograph-
ics, tumour site and staging, impact of treatment modal-
ities on the patient’s ability to meet and sustain
nutritional requirements, nutritional status, dysphagia,
type and placement technique of feeding tube and
S37
associated morbidity.4,9,10 While there is no universally
accepted definition of gastrostomy dependency, the
principle is recognised and reported.15 In clinical
studies, gastrostomy tube is used as a proxy measure
for poor swallowing in the absence of reviewing nutri-
tional outcome data, intensity and frequency of dietary
counselling and swallowing rehabilitation and co-
ordination of these services before, during and after
treatment.9,10
Enteral nutrition
The type and volume of EN will depend upon the
patients’ symptoms and current intake and is likely to
change throughout and following treatment.2 There
are no data to suggest a role for cancer-specific
enteral formulae and standard polymeric feeds should
be used in this population group. There are a range of
nutritionally complete feeds available. Local policies
and feed contract arrangements determine the type
and make.
Immune-enhanced nutrition
Immunonutrition are feeds containing amino acids,
nucleotides and lipids. There are no additional benefits
to immunonutrition pre-operatively over standard nutri-
tion support. Preliminary data suggest that in the peri-
operative period, N-3 enriched nutrition support may
improve nutritional outcomes including weight, lean
body mass and fat mass, reduce post-operative infec-
tions and reduce hospital stay.16
Monitoring nutritional support
Monitoring nutritional intervention is essential, as
compliance with recommendations can be a problem.
Monitoring should involve the multidisciplinary
team, including dietitians, medical teams, speech and
language therapist and clinical nurse specialists.
Recommendations
• Start nutritional therapy if undernutrition
already exists or if it is anticipated that the
patient will be unable to eat for more than 7
days. Enteral nutrition should also be started
if an inadequate food intake (60 per cent of
estimated energy expenditure) is anticipated
for more than 10 days (R)
• Use standard polymeric feed (G)
• Consider gastrostomy insertion if long-term
tube feeding is necessary (greater than four
weeks) (R)
• Monitor nutritional parameters regularly
throughout the patient’s cancer journey (G)
S38
Nutrition considerations during surgical
treatment
Enhanced recovery after surgery programmes are start-
ing to be developed and implemented across Head and
Neck Centres. Nutritional interventions are part of
enhanced recovery and should be considered at all
stages of the pathway from diagnosis to survivorship
and wellbeing.
Pre-operative nutrition
Inadequate oral intake for more than 14 days is asso-
ciated with a higher mortality. Patients with severe
nutritional risk should receive nutrition support for
10–14 days prior to major surgery even if surgery
has to be delayed.5,16 Carbohydrate loading is becom-
ing standard practice in some centres for all patients
undergoing head and neck cancer surgery. It has
been shown to be safe and well tolerated in patients
undergoing head and neck surgery. The type of carbo-
hydrate-loading products used will depend on local
contractual arrangements. Enteral nutrition is indicated
even in patients without obvious undernutrition, if it is
anticipated that patients will be unable to eat for more
than 7 days peri-operatively. Box III indicates
criteria for initiating pre/peri-operative nutrition
support and identifies patients with severe nutritional
risk.
BOX III
CRITERIA FOR INITIATING PRE-OPERATIVE
NUTRITIONAL SUPPORT2,5
Indications:
• Weight loss >10–15 per cent in 6 months
• Body mass index <18.5 kg/m2
• Subjective Global Assessment Grade C
• Serum albumin <30 g/l
• Unable to maintain intake above 60 per cent of
recommended intake for more than 10 days
Post-operative nutrition
Early post-operative tube feeding (within 24 hours) is
indicated in patients in whom early oral nutrition
cannot be initiated. Nutrition support, especially enteral
nutrition, reduces morbidity. In some centres, as part of
the enhanced recovery programme, very early nutritional
intervention is being trialled. Standard polymeric enteral
feeds are suggested post-operatively with currently very
limited evidence to support the use of immunonutrition.
Early oral feeding after primary total laryngectomy (from
as early as 1 day post-operation to 7 days) is thought to
reduce length of stay as there has been shown to be no dif-
ference in fistulae rates compared with delayed oral
feeding of >7 days.
B TALWAR, R DONNELLY, R SKELLY et al.
Nutritional management of chyle leaks
This is a rare complication with an incidence of 1–2 per
cent following radical neck dissections, and less
common with selective neck dissections often per-
formed in current practice. The management may be
conservative, including dietary manipulation or further
surgery. A post-operative leak gives the fluid a milky
appearance. A triglyceride level >110 mg/dl is diag-
nostic of a chyle leak. If the triglyceride level is
<110 mg/dl, further analysis is required to demonstrate
the presence of chylomicrons. A triglyceride level
<50 mg/dl usually rules out a diagnosis of a chyle
leak unless a patient is malnourished or has been fasted.
The principal aims of nutritional management are to
reduce the flow of chyle whilst maintaining nutritional
status, ensuring adequate fluid balance and replacing
electrolyte losses.
The nutritional management is to use a fat free or
high medium chain triglyceride (MCT) product.
Medium chain triglyceride is recommended because
it is directly absorbed into the portal system resulting
in less chyle production. In clinical practice fat free pro-
ducts can be more accessible and practical than MCT
feeds. If dietary manipulation is unsuccessful paren-
teral nutrition may be required. This should not be
used as first line management except in extreme
cases, e.g. very high-volume leaks (>1000 ml).
There is no consensus on how to nutritionally manage
chyle leaks, how long nutrition management should
be pursued, or what constitutes an acceptable amount
of chyle output.1,17,18 The nutritional intervention is
usually dependant on clinician preference.
Recommendations
• Pre-operative:
○ Patients with severe nutritional risk should
receive nutrition support for 10–14 days
prior to major surgery even if surgery has
to be delayed (R)
○ Consider carbohydrate loading in patients
undergoing head and neck surgery (R)
• Post-operative:
○ Initiate tube feeding within 24 hours of
surgery (R)
○ Consider early oral feeding after primary
laryngectomy (R)
• Chyle leak:
○ Confirm chyle leak by analysis of drainage
fluid for triglycerides and chylomicrons (R)
○ Commence nutritional intervention with
fat free or MCT nutritional supplements
either orally or via a feeding tube (R)
○ Consider parenteral nutrition in severe cases
when drainage volume is consistently high (G)
NUTRITIONAL CONSIDERATIONS IN HEAD AND NECK CANCER: UK GUIDELINES
Nutritional considerations during curative
radiotherapy ± chemotherapy
Concomitant mucositis during radiotherapy ± chemo-
therapy results in weight loss, which cannot be com-
pletely prevented by nutritional counselling alone.19
Intensive dietary counselling and oral nutrition
support to increase dietary intake and to prevent treat-
ment associated weight loss is recommended for
patients undergoing radiotherapy of the head and
neck.20 This is also advised to prevent interruptions
to radiation treatment. Tube feeding is recommended
if the cancer interferes with swallowing or if mucositis
is anticipated which may interfere with oral and/or
pharyngeal swallowing.21 The optimal method of
tube feeding remains unclear, therefore, the risks and
benefits of both proactive and reactive approaches
should be discussed by the dietitian with the patient
to ensure individualised nutritional care.1 Prophylactic
tube feeding compared to oral intake alone or reactive
tube demonstrates reduced weight loss in the short
term, may reduce unplanned hospital admissions and
may improve QoL during and after treatment.1 The
Clinical Oncological Society of Australia recommends
that patients should be seen weekly during radiother-
apy. However, in some centres twice weekly follow
up is provided. Intensity Modulated radiotherapy is
now used for the treatment of head and neck cancer.
This treatment has not been found to reduce nutrition
related toxicity and patients should be managed in the
same way as conventional radiotherapy. Patients receiv-
ing biological agents such as cetuximab with radiother-
apy should be nutritionally managed in the same way as
those receiving chemoradiotherapy.1
Recommendations
• Weekly dietetic intervention is offered for all
patients undergoing radiotherapy treatment
to prevent weight loss, increase intake and
reduce treatments interruptions (R)
• Offer prophylactic tube feeding as part of
locally agreed guidelines, where oral nutrition
is inadequate (R)
Nutritional considerations during palliative
chemotherapy and radiotherapy
The use of chemotherapy and radiotherapy may be used
to relieve symptoms caused by the cancer where the goal
is to improve the QoL but not treat the disease. Palliative
chemotherapy and radiotherapy is increasingly used in
the treatment of head and neck cancer and the dietitian
has a role in supporting the nutritional needs of patients
receiving these treatments. Patients may experience
side effects from these treatments which affect their
ability to take adequate nutrition or require dietary
intervention to support their QoL.1,9
S39
Rehabilitation
Patients are at high risk of developing late and long-
term effects of treatment resulting in eating difficulties
requiring dietary modification, supplementation and
alternative feeding. Patients should be seen fortnightly
for at least six weeks post-treatment and patients should
be reviewed by the dietitian for up to six months or for
as long as they require management of chronic toxici-
ties, weight loss or tube feeding.1
Guidance for clinical management and a strategic
framework for structured head and neck ‘local
support’ services as part of the multidisciplinary team
are limited, but should be interpreted at a local level
to deliver high-quality patient-centred nutritional
care.1,4
Recommendation
• Offer nutritional intervention (dietary
counselling and/or supplements) for up to
three months after treatment (R)
Survivorship
The number of patients living with cancer or its long-
term side effects is increasing. Many of our cancer sur-
vivor patients have unmet needs. It is recommended
that patients are offered education and support events
(Health and Wellbeing Clinics) after completion of
treatment and rehabilitation.22 Dietitians can play a
key role in these events by offering tailored healthy
eating advice that takes into consideration the long-
term side effects that head and neck cancer patients
may experience. Macmillan cancer support is currently
developing a healthy eating toolkit that can be adapted
for use with head and neck cancer patients.
Recommendation
• Patients who have completed their
rehabilitation and are disease free should be
offered healthy eating advice as part of a
health and wellbeing clinic (G)
Quality of life
Head and neck-specific validated tools exist to evaluate
QoL. These tools may include factors relating to eating
and drinking, but there is no nutrition-specific module
to assess the relationship between QoL, nutritional
status, malnutrition and nutrition support in this
patient group.4 Reduction in QoL can be directly
related to weight loss and malnutrition with an
improvement seen when dietary counselling and
S40
aggressive nutritional support is maintained during
treatment. The impact of having a feeding tube on
patients’ QoL requires further evaluation.
Recommendation
• Quality of life parameters, including nutrition
and swallowing, should be measured at
diagnosis and at regular intervals post-
treatment (G)
Key points
• Nutrition has an important role in the management
of head and neck cancer and its associated treatment
modalities
• Specialist site specific dietitians should be part of the
multidisciplinary team for treating head and neck
cancer patients as frequent dietetic contact has
been shown to enhance outcomes
• Comprehensive nutritional assessment is necessary
to ensure early recognition of patients who have or
are at risk of developing malnutrition to allow
timely and appropriate intervention
• Nutritional interventions are varied and have an
important role throughout the course of the
disease, from diagnosis through to terminal care
• Effective nutritional interventions should ultimately
aim to improve QoL and enhance the beneficial
effects of treatment.
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Address for correspondence:
Bella Talwar,
Head and Neck Centre,
University College London Hospital NHS Foundation Trust,
London, UK
E-mail: bella.talwar@uclh.nhs.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S41–S44. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000414

Restorative dentistry and oral rehabilitation: United

Kingdom National Multidisciplinary Guidelines

C BUTTERWORTH1, L MCCAUL2, C BARCLAY3

1
Merseyside Regional Head and Neck Cancer Centre, University Hospital Aintree and Liverpool University Dental
Hospital, Liverpool, 2Division of Surgery and Anaesthesia, Bradford Teaching Hospitals NHS Foundation Trust,
Bradford, and 3University Dental Hospital of Manchester, Manchester, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK and provides recommendations on the pre-treatment oral and dental assessment, during and
after treatment and oral rehabilitation. Restorative dentists are core members of the multidisciplinary team
treating head and neck cancer patients, involved from the treatment planning phase through to long-term
rehabilitation.

Recommendations
• Preventative oral care must be delivered to patients whose cancer treatment will affect the oral cavity, jaws,
salivary glands and oral accessibility. (G)
• Close working and communication between the surgeons, oncologists and restorative dental specialists is
important in ensuring optimal oral health outcomes. (G)
• Intensity-modulated radiotherapy has been shown to reduce long-term xerostomia and should be offered to all
appropriate patients. (R)
• If patients are deemed at risk of trismus they should be warned and its progressive and potentially irreversible
nature explained. (G)
• Where it is known that adjuvant radiotherapy will be given, extractions should take place at primary surgery to
maximise the time for healing and minimise the number of surgical events for patients. (G)
• Osseointegrated implants should be considered for all patients having resection for head and neck cancer. (G)

Introduction • Avoidance of unscheduled interruptions to

The consultant in restorative dentistry and oral rehabili-
tation is a core member within the head and neck
cancer team as many patients face complex oral
rehabilitation and dental health issues during and
after their treatment. This section addresses the issues
relating to pre-treatment oral and dental assessment,
preventative advice, during and after treatment and
oral rehabilitation.
Oral and dental assessment prior to
primary treatment
Patients whose oral cavity, teeth, salivary glands and
jaws will be affected should have assessment and
appropriate management as early as possible to allow
time for any necessary dental treatment.1 This should
render patients dentally fit before treatment and
ensure the oral cavity can be maintained and rehabili-
tated after treatment.2
The aims of pre-treatment assessment are:
primary treatment as a result of dental problems
• Pre-prosthetic planning and treatment, e.g. planning
for primary implants and/or impressions for obturator
• Planning for extraction of teeth which are of
doubtful prognosis or are at risk of dental
disease in the future and are in an area where
there would be risk of osteoradionecrosis.2
Extractions to be carried out as early as possible
in the patient journey but, as a minimum, at least
10 days prior to radiotherapy
• Planning for restoration of remaining teeth as
required
• Preventive advice and treatment
• Assess potential for post-treatment access difficul-
ties, e.g. trismus, microstomia.
Treatment side effects
Treatment for head and neck cancer may involve
surgery, chemotherapy and radiotherapy which can
S42
cause adverse short- and long-term oral side effects as
follows:
Short term:
• Mucositis: inflammation and ulceration of the
mucosal lining of the oral cavity
• Infection: chemotherapy-induced neutropenia
makes the patient susceptible to bacterial, viral
and fungal infections. Oral candidal infections
are extremely common following chemotherapy
or radiotherapy
• Xerostomia: dry mouth resulting from a decrease
in the production of saliva as a result of
radiotherapy.
Long term:
• Altered anatomy: surgical ablation and reconstruc-
tion can cause permanent changes in oral anatomy
making prosthetic rehabilitation difficult
• Rampant dental caries: radiogenic dental caries3,4
is thought to be the result of reduced salivary flow
as well as possible direct radiogenic damage to the
amelo-dentinal junction by radiotherapy
• Trismus: may be caused by surgical scarring or by
radiotherapy induced fibrosis of the masticatory
muscles
• Mastication difficulties: if a significant number of
opposing pairs of teeth are lost
• Osteoradionecrosis: hypovascularity and necrosis
of bone followed by trauma-induced or spontan-
eous mucosal breakdown, leading to a non-
healing wound
• Xerostomia: intensity-modulated radiotherapy
(IMRT) reduces the risk of xerostomia after treat-
ment and possibly osteoradionecrosis.5
Management
Preventive management
• Maintenance of good oral hygiene by effective
tooth brushing; flossing daily
• Dietary advice with regard to caries prevention
• Daily topical fluoride application (5000 ppm
fluoride toothpaste) in custom-made trays or
brush-on.6 Daily fluoride mouth rinse, reminera-
lising agents
• Daily use of GC Tooth Mousse™ containing free
calcium or other remineralising agent7
• Saliva replacement therapy and use of frequent
saline rinses
• Jaw exercises to reduce trismus.
Peri-treatment and post-treatment management
Oral mucositis and ulceration. Treatments include
Chinese medicines, hydrolytic enzymes, ice chips, ben-
zydamine, calcium phosphate, etoposide bolus,
manuka honey, iseganan and zinc sulphate.8 All have
C BUTTERWORTH, L McCAUL, C BARCLAY
been shown to demonstrate some level of benefit
although the response seems to be patient specific.
Benzydamine mouthwash has been recommended for
those patients receiving moderate radiation without
concomitant chemotherapy. The use of amifostine in
this setting has now been refuted.
Oral candidal infections. There is strong evidence that
some antifungal drugs prevent oral candidiasis caused
by cancer treatment, but nystatin does not appear to
work. Chlorhexidine gluconate has antifungal and anti-
bacterial properties in addition to antiplaque effects;
however, its value is still unconfirmed. Its tendency
to stain teeth and its alcohol content, which can irritate
inflamed tissues, are potential drawbacks.
Xerostomia. This can be managed by sipping sugarless
fluids frequently, chewing sugarless gum or lozenges,
and using a carboxymethyl cellulose saliva substitute
as a mouthwash. Oral balance gel may be best
accepted by patients because of its extended duration
of effect. Acidic salivary stimulants such as
Glandosane™ should not be used by dentate patients
as their pH is below the critical pH of 5.5.
Pilocarpine (5–10 mg/day) may improve radiation
induced xerostomia in patients with evidence of
some intact salivary function.
Altered anatomy. Prostheses may be required to replace
missing oral and facial tissues. These may be implant
supported.
Rampant dental caries. Management must be individua-
lised, and patients must be assessed at regular intervals
to determine the caries risk and caries activity to
provide guidance for maintenance of the dentition.
Mastication difficulties. This can be minimised by
maintenance of the dentition and use of well-made
prostheses.
Trismus. Jaw exercises and the use of devices such as
the Therabite™ prior to and during radiotherapy may
limit the severity of trismus, but they will not mobilise
fibrosis once it has occurred. They may help surgically
induced trismus (as may coronoidectomy). Dental
work that was deferred during radiotherapy should
be completed. Frequent dental follow-up appoint-
ments (3–4 monthly), either with local general or
community dental practitioner is warranted for these
patients.
Oral rehabilitation using osseointegrated implants.
Osseointegrated implants allow effective oral and
facial rehabilitation following cancer treatment includ-
ing radiotherapy.9,10 They are used to support oral or
facial prostheses.11 Appropriate detailed planning and
patient selection are important prior to proceeding
with treatment. The use of hyperbaric oxygen may be
considered prior to elective implant placement in the
RESTORATIVE DENTISTRY AND ORAL REHABILITATION: UK GUIDELINES
irradiated jaws (>60 Gy) in an attempt to improve
implant survival rates but is a controversial area with
currently no clear cut evidence.
Recommendations
• Preventive oral care must be delivered to
patients whose cancer treatment will affect the
oral cavity, jaws, salivary glands and oral
accessibility (G)
• Close working and communication between
the surgeons, oncologists and restorative
dental specialists is important in ensuring
optimal oral health outcomes (G)
• IMRT has been shown to reduce long-term
xerostomia and should be offered to all
appropriate patients (R)
• If patients are deemed at risk of trismus
they should be warned and its progressive and
potentially irreversible nature explained (G)
• Where it is known that adjuvant radiotherapy
will be given, extractions should take place at
primary surgery to maximise the time for
healing and minimise the number of surgical
events for patients (G)
• Osseointegrated implants should be
considered for all patients having resection for
head and neck cancer (G)
Primary dental implants. The placement of intra-oral
implants at the same time as tumour resection may be
beneficial for carefully selected patients and where
there is continuity of the mandible or in patients who
require the prosthetic obturation of significant maxil-
lary defects where retention of the obturator is likely
to be compromised or in patients undergoing rhinect-
omy or orbital exenteration.9,12 In patients having seg-
mental resection and reconstruction of the mandible,
implant survival and usefulness is improved by
delayed placement after suitable prosthodontic
planning.13
Secondary dental implants. For many patients, the
placement of osseointegrated implants will be consid-
ered following cancer treatment in response to ongoing
problems with oral function. A secondary approach
allows a detailed assessment of the patient’s overall
prognosis, their individual risk factors (alcohol,
smoking, oral hygiene, radiotherapy, etc.) as well as
their anatomical factors such as the presence of recon-
structive hard and soft tissue grafts, metal hardware,
tongue function and mouth opening. Comprehensive
prosthodontic planning should be undertaken prior to
surgery and the use of computerised planning and surgi-
cal guide stent technology is useful.
S43
Key points
• Consultants in Restorative Dentistry are core
members of the multidisciplinary team dealing
with head and neck cancer patients
• Patients whose oral cavity, teeth, salivary glands and
jaws will be affected by their treatment should have a
dental assessment and appropriate management as
early as possible to allow time for any necessary
dental treatment
• Patients requiring maxillary obturation should be
carefully prepared for treatment by a Restorative spe-
cialist who should ideally be present during surgery
• Consideration should be given to the placement of
osseointegrated titanium implants at the time of
primary resective surgery in selected patients in
order to support dental and facial prostheses
• Liaison with the patient’s general dental practitioner
is important for ongoing dental care with support
from the Restorative specialist where advice is
required.
References
1 Shaw MJ, Kumar ND, Duggal M, Fiske J, Lewis DA, Kinsella T
et al. Oral management of patients following oncology treat-
ment: literature review. Br J Oral Maxillofac Surg 2000;38:
519–24
2 Dewan K, Kelly RD, Bardsley P. A national survey of consul-
tants, specialists and specialist registrars in restorative dentistry
for the assessment and treatment planning of oral cancer
patients. Br Dent J 2014;216:E27
3 Silva AR, Alves FA, Berger SB, Giannini M, Goes MF, Lopes
MA. Radiation-related caries and early restoration failure in head
and neck cancer patients. A polarized light microscopy and
scanning electron microscopy study. Support Care Cancer
2010;18:83–7
4 Kielbassa AM, Hinkelbein W, Hellwig E, Meyer-Luckel H.
Radiation-related damage to dentition. Lancet Oncol 2006;7:
326–35
5 Ben-David MA, Diamante M, Radawski JD, Vineberg KA,
Stroup C, Murdoch-Kinch CA et al. Lack of osteoradionecrosis
of the mandible after intensity-modulated radiotherapy for head
and neck cancer: likely contributions of both dental care and
improved dose distributions. Int J Radiat Oncol Biol Phys
2007;68:396–402
6 Epstein JB, van der Meij EH, Lunn R, Stevenson-Moore P.
Effects of compliance with fluoride gel application on caries
and caries risk in patients after radiation therapy for head and
neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 1996;82:268–75
7 Papas A, Russell D, Singh M, Kent R, Triol C, Winston A.
Caries clinical trial of a remineralising toothpaste in radiation
patients. Gerodontology 2008;25:76–88
8 Worthington HV, Clarkson JE, Bryan G, Furness S, Glenny
AM, Littlewood A et al. Interventions for preventing oral muco-
sitis for patients with cancer receiving treatment. Cochrane
Database Syst Rev 2011;CD000978
9 Barber AJ, Butterworth CJ, Rogers SN. Systematic review of
primary osseointegrated dental implants in head and neck oncol-
ogy. Br J Oral Maxillofac Surg 2011;49:29–36
10 Schiegnitz E, Al-Nawas B, Kammerer PWGrotz KA. Oral
rehabilitation with dental implants in irradiated patients: a
meta-analysis on implant survival. Clin Oral Investig 2014;18:
687–98
11 Korfage A, Raghoebar GM, Slater JJ, Roodenburg JL, Witjes
MJ, Vissink A et al. Overdentures on primary mandibular
implants in patients with oral cancer: a follow-up study over
14 years. Br J Oral Maxillofac Surg 2014;52:798–805
12 Mizbah K, Dings JP, Kaanders JH, van den Hoogen FJ,
Koole R, Meijer GJ et al. Interforaminal implant placement
S44 C BUTTERWORTH, L McCAUL, C BARCLAY

in oral cancer patients: during ablative surgery or delayed? A Address for correspondence:
5-year retrospective study. Int J Oral Maxillofac Surg 2013; Chris Butterworth,
42:651–5 Merseyside Regional Head and Neck Cancer Centre,
13 Fenlon MR, Lyons A, Farrell S, Bavisha K, Banerjee A, Palmer University Hospital Aintree & Liverpool University
RM. Factors affecting survival and usefulness of implants Dental Hospital,
placed in vascularized free composite grafts used in post-head Liverpool, UK
and neck cancer reconstruction. Clin Implant Dent Relat Res
2012;14:266–72 E-mail: c.butterworth@liverpool.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S45–S48. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000426

Psychological management for head and neck

cancer patients: United Kingdom National
Multidisciplinary Guidelines

G HUMPHRIS

University of St Andrews, Medical School, North Haugh, St Andrews, Fife, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. It provides recommendations on the assessment and interventions for the psychological
management in this patient group.
Recommendations
• Audit of information supplied to patients and carers should be conducted on an annual basis to update and
review content and media presentation. (G)
• Patients and carers should be invited to discuss treatment options and relate possible outcomes to functional
retention or loss to provide a patient-centred approach. (G)
• Clinical staff should inspect their systems of assessment to make them sensitive enough to identify patients
with psychological difficulties. (G)
• Flexibility, rather than rigid formulation is required to assess patients frequently, and to allow for change in
circumstances to be noted. (G)
• Multidisciplinary teams should determine the supportive care services available and commission extra
assistance to provide patients and carers with timely information, education or brief supportive advice. (G)
• Multidisciplinary teams need to inspect specialist services for mental health interventions at structured and
complex levels for the small proportion of patients with more serious, but rarer, psychological difficulties. (G)
• Clinical staff at all levels should receive communication skills training to raise and maintain consultation
expertise with difficult patient and/or carer interactions. (G)

Introduction Communication of diagnosis and treatment

The head and neck cancer patient and their carers have
considerable challenges to overcome.1 The psycho-
logical experience of the patient with head and neck
cancer has been closely described in a recent systematic
review and meta-synthesis.2 Although many patients
appear to cope surprisingly well, a sizeable minority
experience considerable psychological effects includ-
ing uncertainty about the return of cancer, disruption
to daily life, a diminished self, attempts to understand
the changes that occur and finding a plan forward.
Treatment recovery may be hampered by mood
changes, whereas longer term psychological states
may feature some months and even years following
initial treatment.3 This section has benefited from
recent research in the field and highlights the major
psychological management concerns in the course of
caring for the patient being treated for head and neck
cancer.4
Evidence from other areas of treating cancer at other
sites has demonstrated clearly that the way in which
the diagnosis is presented to the patient is important
to their psychological response to the disease and treat-
ment.5,6 It is vital that the patient is told explicitly that
they have a cancer, its nature and that all treatment
available is presented to them in an unambiguous
manner. This needs to be relayed consistently by all
members of the team, so that the patient and carer are
able to draw upon their coping abilities as well as pos-
sible. Recent evidence shows that delivering informa-
tion without interruption, avoiding jargon and
showing appropriate empathy are important features
of the diagnostic interview to help prevent illness con-
cerns developing.6 Decision-making and designing
tools to improve communication between clinician and
patient is improving rapidly and highlights an important
growth area for the future of head and neck cancer care
S46
where complex choices are discussed and commitments
made with patients.7,8
Delivering information about treatment
and recovery
Considerable efforts have been expended to determine the
information needs of head and neck cancer patients.9,10
Poor satisfaction with information supplied by the
team was predictive of patient lowered mood and
quality of life (QoL) in the longer term.11 More infor-
mation was required on financial advice, support
groups and ability to return to work. Virtually no
studies have been reported on patient desire to be
involved in treatment decision making. The nature of
the disease and its complex profile of mixed treatment
methods have favoured the multidisciplinary team’s
(MDT) sole authority to determine treatment regimens.
However, recent reports have compiled large datasets
of ‘normative’ QoL estimates linked to various treat-
ment options, which enable the team to start sharing
the potential risks and benefits of certain treatment
packages and tailoring to patient preferences of
retained functions on recovery.12
Recommendations
• Audit of information supplied to patients and
carers should be conducted on an annual
basis to update and review content and media
presentation (G)
• Patients and carers should be invited to
discuss treatment options and relate possible
outcomes to functional retention or loss to
provide a patient-centred approach (G)
Managing psychological distress
The use of routine assessments for psychological dis-
tress such as the Distress Thermometer and the
Hospital Anxiety and Depression Scale are being con-
sidered as a means to identify those patients who may
suffer during the process of treatment preparation, the
treatment itself, initial stages of recovery and follow-
up out-patient appointments.13 These assessments
have the ability to capture those patients who would
not necessarily be identified by the MDT as needing
psychological support.14 Two issues follow however:
an increased number of patients in need of assistance;
and screening measures that may indicate substantial
distress when there is none due to measurement error.
The types of psychological distress require attention
and definition. The classical typology of mental dis-
tress includes anxiety and depression. In addition,
assessments of recurrence fears (the most frequent
reported concern of head and neck cancer patients),
facial disfigurement, body image, loneliness and
sexual dysfunction may also be compiled within an
G HUMPHRIS
MDT assessment profile library for occasional use
when required.15,16 Recurrence fears have been found
to be linked closely to depression in patients and
some evidence exists that patients can stimulate these
fears in their carers.17 Furthermore, it is now recognised
that high recurrence fears promote more requests for
medical services incurring higher treatment and sur-
veillance costs. Acknowledgement of the patient
experience of the severity and longevity of these fears
is important and more in-depth approaches may be
required to alleviate debilitating distress.18
The profile of staff expertise and skills needs close
inspection to enable a flexible and tailored matching
of need to professional training of support or specialist
staff. Multidisciplinary teams need to plan their ser-
vices to provide escalating level of care according to
the specific need of psychological difficulty presented
by the patient. The newly developing Map of
Medicine describes in detail the levels of intervention
(1–4). Timely support and educational approaches are
conducted at levels 1 and 2. Structured interventions
are provided at level 3 by staff with a mental health
qualification. Level 4 interventions consisting of
complex psychotherapeutic approaches are delivered
by clinical psychologists, counselling psychotherapists
and liaison psychiatrists.
Recommendations
• Clinical staff should inspect their systems of
assessment to make them sensitive enough to
identify patients with psychological
difficulties (G)
• Flexibility, rather than rigid formulation is
required to assess patients frequently, and
to allow for change in circumstances to be
noted (G)
• Multidisciplinary teams should determine the
supportive care services available and
commission extra assistance to provide
patients and carers with timely information,
education or brief supportive advice (G)
• Multidisciplinary teams need to inspect
specialist services for mental health
interventions at structured and complex levels
for the small proportion of patients with more
serious, but rarer, psychological difficulties (G)
Family and social support
It is important for the MDT to raise survivorship issues
with patients.19 Not only does the patient remain
watchful for indicators and symptoms that may raise
concern for life reducing disease processes, but also
to maintain function for as long as possible. Two
areas are pertinent here. Firstly carers and spouses
PSYCHOLOGICAL MANAGEMENT FOR HEAD AND NECK CANCER PATIENTS: UK GUIDELINES
should be encouraged to use techniques to enhance
adherence of follow-up MDT recommendations.
Second and closely related is the use of social media
to link other members of the local community with
similar health conditions and survivorship concerns
who can share information and provide extended
social support outside the hospital boundaries.
End of life issues
Communication with the patient assumes even greater
importance when curative treatment options are
not available and care focuses towards a palliative
approach.20 Areas such as assessing patient prefer-
ences concerning life expectancy, control of pain,
and managing fears of uncertainty and family reactions
are features of these discussions with the staff of the
MDT and palliative care services. The psychological
burden to staff requires recognition, supervision and
training.
Recommendation
• Clinical staff at all levels should receive
communication skills training to raise and
maintain consultation expertise with difficult
patient and/or carer interactions (G)
Key points
• Develop information services for patients and carers.
Consider introducing new technology to collect
routine patient self-report data on health behaviour,
psychological responses to care received, outlining
of key messages and outcome assessments
• Develop decision-making tools (such as explanatory
tablet applications) for the aid of patients to enter
into discussion with multidisciplinary team to
agree on treatment plan
• Collect routine psychological assessments at key
points during course of care. These indicators must
be supported with dedicated and tailored interventions
to prevent neglect of identified psychological distress
or depression
• Focus on level of support and intervention that
current team can realistically provide with current
level of resource. Remain cautious when introducing
change, but strengthen and build upon supports
already available
• Develop more comprehensive support services by
improving generic communication skills training for
current staff and ensure consistency of message
giving to patients and/or carers across the multidiscip-
linary team
• Introduce staff training to assist with management of
potential burnout in multidisciplinary team staff.
Consider flexible responses including secondments,
study breaks and peer-support programmes
S47
• Audit current psychological services applied in the
head and neck cancer service. Identify current
usage, gaps in service and develop forward plans
to address these gaps
• Assess current capability of specialist clinical nurse
skills to support head and neck cancer patients psy-
chologically, and introduce dedicated training and
supervision programmes
• Actively search for clinical psychology service input
and negotiate improved access and response time.
Estimate likely demand of service
• Consider appointing sessional input to cancer
network of a clinical or counselling psychologist or
psychotherapist
• Identify liaison psychiatry service and negotiate
referral pathway and response time.
References
1 Wells M, Cunningham M, Lang H, Swartzman S, Philp J, Taylor
L et al. Distress, concerns and unmet needs in survivors of head
and neck cancer: a cross-sectional survey. Eur J Cancer Care
(Engl) 2015;24:748–60 Epub 2015/08/08
2 Simard S, Thewes B, Humphris G, Dixon M, Hayden C,
Mireskandari S et al. Fear of cancer recurrence in adult cancer
survivors: a systematic review of quantitative studies.
J Cancer Surviv Res Pract 2013;7:300–22 Epub 2013/03/12
3 Hammerlid E, Ahlner-Elmqvist M, Bjordal K, Biorklund A,
Evensen J, Boysen M et al. A prospective multicentre study in
Sweden and Norway of mental distress and psychiatric morbidity
in head and neck cancer patients. Br J Cancer 1999;80:766–74
4 Humphris G. The missing member of the head and neck multi-
disciplinary team – the psychologist! Why we need them! Curr
Opin Otolaryngol Head Neck Surg 2008;16:108–12
5 Badr H, Carmack CL, Diefenbach MA. Psychosocial interven-
tions for patients and caregivers in the age of new communica-
tion technologies: opportunities and challenges in cancer care.
J Health Commun 2015;20:328–42 Epub 2015/01/30
6 Back AL, Arnold RM, Baile WF, Fryer-Edwards KA, Alexander
SC, Barley GE et al. Efficacy of communication skills training
for giving bad news and discussing transitions to palliative
care. Arch Intern Med 2007;167:453–60
7 Newton JT. Reactions to cancer: communicating with patients,
family and carers. Oral Oncol 2010;46:442–4
8 Austin CA, Mohottige D, Sudore RL, Smith AK, Hanson LC.
Tools to promote shared decision making in serious illness: a
systematic review. JAMA Inter Med 2015;175:1213–21 Epub
2015/05/20
9 Chen SC, Lai YH, Liao CT, Chang JTC, Lin CC. Unmet infor-
mation needs and preferences in newly diagnosed and surgically
treated oral cavity cancer patients. Oral Oncol 2009;45:946–52
10 Humphris GM, Ozakinci G. Psychological responses and
support needs of patients following head and neck cancer. Int
J Surg 2006;4:37–44 Epub 2007/04/28
11 Llewellyn CD, McGurk M, Weinman J. How satisfied are head
and neck cancer (HNC) patients with the information they
receive pre-treatment? Results from the satisfaction with
cancer information profile (SCIP). Oral Oncol 2006;42:726–34
12 Ethunandan M, Rennie A, Hoffman G, Morey P, Brennan P.
Quality of dying in head and neck cancer patients: a retrospect-
ive analysis of potential indicators of care. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 2005;100:147–52
13 Mitchell AJ. Pooled results from 38 analyses of the accuracy of
distress thermometer and other ultra-short methods of detecting
cancer-related mood disorders. J Clin Oncol 2007;25:4670–81
14 Semple CJ, Dunwoody L, Kernohan WG, McCaughan E.
Development and evaluation of a problem-focused psychosocial
intervention for patients with head and neck cancer. Support
Care Cancer 2009;17:379–88
15 Hodges LJ, Humphris GM. Fear of recurrence and psychologic-
al distress in head and neck cancer patients and their carers.
Psychooncology 2009;18:841–8
S48 G HUMPHRIS

16 Hagedoorn M, Molleman E. Facial disfigurement in patients 20 Sciubba J. End of life considerations in the head and neck cancer
with head and neck cancer: the role of social self-efficacy. patient. Oral Oncol 2009;45:431–4
Health Psychol 2006;25:643–7
17 Rogers S, Scott B, Lowe D, Ozakinci G, Humphris G. Fear of
recurrence following head and neck cancer in the out-patient Address for correspondence:
clinic. Eur Arch Otorhinolaryngol 2010;267:1943–9 Gerry Humphris,
18 Gross SE, Nitzsche A, Gloede TD, Ansmann L, Street R, Pfaff H University of St Andrews,
et al. The initial clinical interview – can it reduce cancer patients’ Medical School,
fear? Support Care Cancer 2015;23:977–84 Epub 2014/09/26 North Haugh,
19 Badr H, Yeung C, Lewis MA, Milbury K, Redd WH. An obser- St Andrews,
vational study of social control, mood, and self-efficacy in Fife KY16 9TF, UK
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Health 2015;30:783–802 Epub 2014/12/05 E-mail: gmh4@st-andrews.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S49–S52. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000438

Quality of life considerations in head and neck

cancer: United Kingdom National Multidisciplinary
Guidelines

S N ROGERS1,2, C SEMPLE3, M BABB4, G HUMPHRIS5

1
Evidence-Based Practice Research Centre, Faculty of Health, Edge Hill University, Ormskirk, 2Regional
Maxillofacial Unit, Aintree University Hospitals NHS Foundation Trust, Liverpool, 3Department of Head and
Neck Cancer, Cancer Services, South Eastern Health & Social Care Trust, Belfast, 4NCRI Head and Neck Clinical
Studies Group, NCIN Head and Neck Site Specific Clinical Reference Group, B16 – Complex Head and
Neck Clinical Reference Group, Chesterfield, Derbyshire, and 5Medical School, University of St Andrews,
St Andrews, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. It identifies the current evidence base and role of health-related quality of life assessment for
this group of patients.

Recommendations
• Health-related quality of life is integral to treatment planning, refining treatment protocols, and more
personalised follow-up support. (G)
• Health-related quality of life and patient concerns should be regularly assessed during patient care. (G)
• Health-related quality of life assessment and patient concerns on an individual patient basis can be helpful to
trigger multi-professional support and interventions. (G)

The evaluation of the quality of life (QoL) in patients
with head and neck cancer is integral to optimal
patient care.1 Survival is usually the initial primary
concern of patients and the focus is on treatments that
offer the best chance of cure as a priority. However,
after treatment there tends to be a shift towards QoL
and living with the consequences of head and neck
cancer treatment (survivorship).
What is quality of life?
Quality of life is a multifaceted construct comprising
many different aspects leading to numerous definitions.
The World Health Organization defines quality of life
as an “individual’s perception of their position in life
in the context of the culture and value systems in
which they live and in relation to their goals, expecta-
tions, standards and concerns”.2 Quality of life com-
prises a person’s physical health and functioning,
psychological state, level of independence, social rela-
tionships, occupation and finance, and personal beliefs.
There is a complex relationship between factors such as
the characteristics of the individual with respect to
symptoms, personality, motivation, value preferences
and the characteristics of the environment such as
psychological, social and economic support.2 The
term ‘health-related quality of life’ (HRQoL) is more
disease specific and allows the healthcare professions
to focus upon the assessment of the impact of the
disease and its treatment on the physical, psychological
and social aspects.3
Why should we measure quality of life?
Health-related quality of life evaluation gives an indica-
tion of how the patient perceives the impact of their
cancer and its treatment. This information can be
used to give the patient and their family an indication
of ‘what will I be like’.1 This patient reported
outcome allows the health professional an opportunity
to reflect on the patient’s reaction. Individual patient-
rated outcomes can often differ quite markedly from
clinician-rated scores. Health-related quality of life
measurement has a role in evaluating treatment out-
comes, helping to define treatment protocols, as
primary or secondary outcome(s) of clinical trials, pro-
viding additional information to assist in individual
decision-making processes, to support the identifica-
tion of poor outcomes, so that intervention and
support can be considered.4 Checklists such as the
S50
Patients Concerns Inventory help patients express
unmet concerns and can be used as part of holistic
needs assessment.5 A better understanding of patients’
perception helps facilitate improvements in aftercare
and serves to drive clinically relevant outcomes
research.6 Also patient-reported outcomes should be
part of national outcome datasets.7–9
It is appreciated that there are many potential diffi-
culties in assessing HRQoL in clinical practice.10,11
Perhaps the biggest challenges are: (i) the burden of
administration and processing of the questionnaires;
(ii) the reality that patients tend to adapt over time, so
that expected differences between treatments might
not be as significant as anticipated; (iii) that HRQoL
data are weighted to survivors; and (iv) that there is
little evidence of agreed standards of analysis and
reporting. Another barrier is the lack of evidence as
to when HRQoL should have a major role on treatment
decisions, or an important role simply as an additional
factor, or perhaps where it has relatively little value.
Hence, healthcare professionals can unrealistically
rely too much on the value of HRQoL in certain clin-
ical situations and this can lead to frustration and a
perceived lack of benefit in the HRQoL process.
How should it be measured?
The commonest way to measure HRQoL is by patient
self-completed questionnaire (quantitative) although
other methods include open and semi-structured inter-
view (qualitative).11 There is no gold standard ques-
tionnaire and each has its own unique features and
merits.12–14 All questionnaires are inherently limited
by the range of issues addressed, the wording used,
and the scoring systems. The choice of questionnaire
depends on the reason for using it, e.g. research,
audit, integrated into routine clinical practice or to
assist in the evaluation of a specific functional
outcome.15
Questionnaires can be used either cross-sectionally
or longitudinally. Longitudinal data from pre-treatment
has the distinct advantage of allowing the measurement
of change and also recording HRQoL during the differ-
ent phases of treatment. It is a logistical challenge to
ensure patients self-complete questionnaires before
treatment and at regular intervals subsequently.
Cross-sectional evaluation is simpler to conduct and
easier to achieve larger patient numbers when stratify-
ing for patient characteristics. Questionnaires can be
divided into four main categories: (i) those asking on
a range of broad issues not specific to cancer; (ii)
those addressing issues common to all cancers; (iii)
questionnaires with items specific to head and neck
cancer; and (iv) those questionnaires that focus in
detail on a particular aspect of head and neck function.9
With changes in treatments e.g. epidermal growth
factor receptor inhibitors as part of chemotherapy, so
existing HRQoL questionnaires might need to be
modified to include additional side effects and func-
tional deficits. As the relationship between unmet
S N ROGERS, C SEMPLE, M BABB et al.
need and HRQoL becomes more clearly understood,
further consideration needs to be given as to how,
within the financial constraints of cancer care, ques-
tionnaires can be more easily integrated into routine
practice. Advances in technology will assist in the col-
lection and inclusion of patient-reported outcomes.
The almost ubiquitous ownership of mobile phones
allows developers in partnership with clinical research-
ers to construct ‘Apps’ that can send alerts to patients
for HRQoL updates on certain features. This is an
exciting area that is in its infancy but holds great
promise to enable a more comprehensive, flexible
and frequent opportunity to explore, study and inter-
vene in patient HRQoL.
What are the key issues?
There are a considerable range of issues that impact on
the HRQoL outcomes following head and neck cancer.
This section makes only very brief comment on the
type of issues involved (listed in alphabetical order).
There are several review articles that give additional
information.12–14,16,17 At the present time there tends
to be a lack of long-term outcomes reported in the lit-
erature. Also newer treatment strategies are under
reported given the time necessary to get adequate
HRQoL information.
• Carer: there is a need to promote positive carer
support; carers can underestimate the HRQoL
outcome
• Comorbidity: patient perception of disability,
rather than the extent and severity of disease is
of major influence in head and neck HRQoL
• Coping: social support seeking is beneficial whilst
avoidance is bad
• Dental status: eating – social interaction and is
linked to coping
• Disfigurement: appearance, body image, not only
an issue in surgical patients
• Emotion: anxiety is high pre-treatment; mood dis-
turbance and/or depression is treatable
• Family and children: the impact of cancer affects
family and community
• Fatigue: common in the first year post-treatment;
poor sleep; low energy
• Fear of recurrence: unpredictable by clinical
characteristics; does not lessen over time; and
high levels predict higher consumption of formal
healthcare.
• Financial and work: employment; benefits; cost of
treatment and follow-up; and retirement
• Function: pre-existing comorbidities; problems of
combination treatment modalities – impact on
recreation, hobbies, interests. In general, the less
the consequence of the cancer and its treatment
in terms of social function the better the HRQoL
outcomes
• Fungating wounds: difficulties in palliation in
head and neck; relatively few published papers
QUALITY OF LIFE CONSIDERATIONS IN HEAD AND NECK CANCER: UK GUIIDELINES
• Information: varying amounts, in various ways, at
different times the importance of communication
skills and consistency of contact with named
health professional for duration of clinical treatment;
also access to patient and career support groups
• Intimacy: sexuality, worst in the younger patient
as an unmet need
• Lifestyle choices: smoking; alcohol abuse
• Nutrition: low weight; diet; gastrostomy feeding
• Oral rehabilitation: chewing and/or eating – realis-
tic expectations of rehabilitation
• Osteoradionecrosis: associated with pain; trismus;
poor HRQoL; and nutrition problems
• Pain: need for opiates; poor sleep; linked with
depression
• Personality: optimism and HRQoL and survival;
high neuroticism poor HRQoL
• Self-esteem: social concerns; reactions of friends,
wider community, work colleague; low self-
esteem associated with poor HRQoL
• Sociodemographic: deprivation and social support;
age; and finance
• Speech: complex function; various aspects; laryn-
geal speech outcomes; isolation
• Swallowing: nutrition; social; presence of feeding
tube most significant to HRQOL
• Shoulder: shoulder discomfort and neck tightness;
debate around avoiding a neck dissection or carry-
ing out a selective dissection
• Trismus: difficulty in mouth opening associated
with diet, social, and dental health
• Unknown: clinical art of the individual patient not
a precise science
• Xerostomia: dry mouth has a profound impact on
social function and HRQoL, intensity modulated
radiation therapy should be used whenever feasible.
Examples of how HRQoL might change
practice
Health-related quality of life is a factor that is weighed
against treatment burden and toxicity, and also any sur-
vival benefit between treatments. In the three common
head and neck cancer sites, HRQoL might be a driver
for evolving strategies alongside other drivers such as
survival, function and healthcare cost. Examples are
described below.
Oropharynx
1. Early stage disease: There is an argument for
transoral excision for early oropharynx lesions
with selective neck dissection. This avoids the
need for free tissue transfer and access procedures
such as lip split mandibulotomy.
Drivers for change: Health-related quality of life,
survival, function, cost to National Health
Service (reduced length of stay).
2. Advanced stage disease: Chemoradiotherapy is
often advocated for larger oropharyngeal primaries
S51
if laser resection is not possible. The long-term
outcomes remain unclear as does the success of
salvage surgery and its impact on HRQoL. The
benefit of salvage surgery and the impact on
HRQoL is currently unclear. Transoral surgery is
problematic due to the high-risk of local necrosis,
non-healing and catastrophic bleeding. The use of
free flap reconstruction in the post-chemora-
diotherapy failures, is often associated with poor
functional outcomes, poor HRQoL and limited
cure rates.
Drivers for change: Health-related quality of life;
function; healthcare cost.
3. Human papilloma virus (HPV) testing: It is con-
ceivable that it is possible to de-escalate treatment
in some HPV positive patients. Similar survival
outcomes may be achieved by the use of cetuxi-
mab and radiotherapy rather than platinum-
based chemoradiotherapy.
Drivers for change: Health-related quality of life.
Larynx
1. Early stage disease: Laser excision rather than
primary radiotherapy for suitable lesions.
Drivers for change: Patient choice based on
equivalent HRQoL and survival.
2. Advanced stage disease: There is debate about
chemoradiotherapy or laryngectomy. Following
chemoradiotherapy the success and impact of lar-
yngectomy for salvage remains to be fully deter-
mined.
Drivers for change: Health-related quality of life,
survival.
Oral cavity
1. Early stage disease: There is a rationale towards
primary surgery without free tissue reconstruc-
tion accepting close margins with low risk of
local recurrence
Drivers for change: Health-related quality of life,
survival, function, cost of overall treatment.
2. Advanced stage disease: Primary surgery with
free tissue reconstruction as required. However,
there is discussion around the benefit of adjuvant
radiotherapy.
Drivers for change: Health-related quality of life,
survival.
Conclusion
The place of HRQoL assessment in head and neck
cancer practice has become more defined in the last
decade. It has had a major role in helping to shape treat-
ment strategies and patient support. More evidence is
yet to emerge to improve guidance as to how to use
HRQoL at an individual patient level and also reflect
the trade off between marginal survival improvements
and increased treatment burden and poorer HRQoL.
Advances in information technology will make it
S52
easier for HRQoL to assist in decision making, delivery
of information, identification of problem areas, the iden-
tification of risk groups, and to drive support and inter-
ventions aimed at improving the HRQoL outcomes.
Recommendations
• Health-related quality of life is integral to
treatment planning, refining treatment
protocols, and more personalised follow-up
support (G)
• Health-related quality of life and patient
concerns should be regularly assessed during
patient care (G)
• Health-related quality of life assessment and
patient concerns on an individual patient
basis can be helpful to trigger multi-
professional support and interventions (G)
Directions for the future
1. Holistic assessment integrated into clinical prac-
tice and patient reported outcomes reported in
national datasets.
2. Survivorship issues addressed through interven-
tions and empowering patients to develop skills
and confidence for self-management.
3. Evidence base related to interventions, e.g.
AFTER intervention for fear of recurrence.
4. A better understanding of late effects of treatment.
5. Partnership and marital issues are no doubt of sig-
nificant importance, as well as grandparents and
children (family). Interventions need to include
couple therapy and family therapy and practi-
tioners need to be trained in these approaches as
well as individual counselling etc.
6. Wider use of information technology to allow
HRQoL and patient concerns to be more readily
available in clinics and across the multi-profes-
sional team.
References
1 Rogers SN, Hogg ES, Cheung WK, Lai LK, Jassal P, Lowe D
et al. ‘What will I be like’ after my diagnosis of head and
neck cancer? Eur Arch Otorhinolaryngol 2015;272:2463–72
S N ROGERS, C SEMPLE, M BABB et al.
2 Saxena S, Orley J. Quality of life assessment: the world health
organization perspective. Eur Psychiatry 1997;12:263–6
3 Wilson IB, Cleary PD. Linking clinical variables with health-
related quality of life. A conceptual model of patient outcomes.
JAMA 1995;273:59–65
4 Rogers SN. Oral Cancer Management: Pitfalls and Solutions.
Article: Rogers SN Quality of life of head and neck cancer
patients. Has treatment planning altered? Oral Oncol 2009;45:
435–9
5 Rogers SN, El-Sheikha J, Lowe D. The development of a
Patients Concerns Inventory (PCI) to help reveal patients con-
cerns in the head and neck clinic. Oral Oncol 2009;45:555–61
6 Rogers SN. Quality of life perspectives in patients with oral
cancer. Oral Oncol 2010;46:445–7
7 Rogers SN, Kanatas A. Assessment of outcomes in quality of
life for head and neck cancer patients. In: Kazi R, Rhys-Evans
P, Harrington KJ, eds. Issues in Head and Neck Cancer.
Dwivedi RC. Byword Books Private Limited, Delhi 2012;
117–25, ISBN 978-81-8193-076-7
8 Sayed SI, Elmiyeh B, Rhys-Evans P, Syrigos KN, Nutting CM,
Harrington KJ et al. Quality of life and outcomes research in
head and neck cancer: a review of the state of the discipline
and likely future directions. Cancer Treat Rev 2009;35:397–402
9 Laraway DC, Rogers SN. A structured review of journal articles
reporting outcomes using the University of Washington Quality
of Life Scale. Br J Oral Maxillofac Surg 2012;50:122–31
10 Rogers SN, Ahad SA, Murphy AP. A structured review and
theme analysis of papers published on ‘quality of life’ in head
and neck Cancer: 2000 to 2005. Oral Oncol 2007;43:843–68
11 Aaronson NK, Bullinger M, Ahmedzai S. A Modular approach
to quality-of-life assessment in cancer clinical trials. Recent
Results Cancer Res 1988;111:231
12 Kanatas AN, Rogers SN. A guide to the questionnaires used in
the measurement of health-related quality of life in head and
neck oncology. Tumori 2008;94:724–31
13 Kanatas AN, Mehanna H, Lowe D, Rogers SN. A second
national survey of health-related quality of life questionnaires
in head and neck oncology. Ann R Coll Surg Engl 2009;91:
420–5
14 Kanatas AN, Rogers SN. A national survey of health-related
quality of life questionnaires in head and neck oncology. Ann
R Coll Surg Eng 2004;86:6–10
15 Rogers SN, Lowe D. Screening for dysfunction to promote
MDT intervention using the University of Washington Quality
of Life questionnaire (UW-QOL). Arch Otolaryngol Head
Neck Surg 2009;135:369–75
16 Ojo B, Genden EM, Teng MS, Milbury K, Misiukiewicz KJ,
Badr H. A systematic review of head and neck cancer quality
of life assessment instruments. Oral Oncol 2012;48:923–37
17 Rogers SN. Quality of life. Chapter 10. Stell and Maran’s
Textbook of Head and Neck Surgery and Oncology, 5th edn,
Eds Watkinson J and Gilbert RW. Taylor and Francis Group
LLC, Boca Raton, FL, 2012: 182–94. ISBN 978-0-340-92916-2
Address for correspondence:
Simon N. Rogers,
Evidence-Based Practice Research Centre,
Faculty of Health, Edge Hill University,
Ormskirk and Regional Maxillofacial Unit,
Aintree University Hospitals NHS Foundation Trust,
Liverpool, UK
E-mail: snrogers.aintree@gmail.com
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S53–S58. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S002221511600044X

Tumour assessment and staging: United Kingdom

National Multidisciplinary Guidelines

N ROLAND1, G PORTER2, B FISH3, Z MAKURA4

1
Department of ENT – Head & Neck Surgery, University Hospital Aintree, Liverpool, 2Department of ENT – Head
& Neck Surgery, University Hospitals Bristol, 3Department of Otolaryngology – Head & Neck Surgery, Cambridge
University Teaching Hospitals Trust, and 4Head & Neck Unit, Queen Victoria Hospital NHS Foundation Trust,
East Grinstead, UK

Abstract
In general, the first decision to be made in a patient with a confirmed head and neck cancer is whether or not to treat
the patient before deciding what form of management strategy is appropriate. There is no more important an aspect
of head and neck cancer care than the initial evaluation of the patient and the patient’s tumour. The practice requires
specific expertise and judgement. The current tumour–node–metastasis system relies on morphology of the tumour
(anatomical site and extent of disease) but the final decision on treatment hinges on a full assessment of the patient
including physiological age and general condition. The aim of this paper is primarily to describe why and how we
appraise a patient and their tumour. It addresses the general principles applicable to the topic of evaluation,
classification and staging. In addition, the limitations and pitfalls of this process are described.

Recommendations
• All patients with head and neck cancer (HNC) should undergo tumour classification and staging prior to
treatment. (R)
• Pre-therapeutic clinical staging of HNCs should be based on at least a C2 factor (evidence obtained by
special diagnostic means, e.g. radiographic imaging (e.g. computed tomography, magnetic resonance
imaging or ultrasound scan), endoscopy, biopsy and cytology). (R)
• Imaging to evaluate the primary site should be performed prior to biopsy to avoid the effect of upstaging
from the oedema caused by biopsy trauma. (G)
• Panendoscopy is only recommended for symptomatic patients or patients with primary tumours known to
have a significant risk of a second (synchronous) primary tumour. (G)

Introduction correspond in their 7th editions (2009) and have

There are many aspects affecting the outcome of patients
with malignant head and neck tumours. These may
relate to the tumour (e.g. the anatomical site and extent
of the disease), the host (age, general condition and
any concurrent disease) and management (treatment
options, expertise available and patient preference).
Staging of head and neck cancer (HNC) is a system
designed to express the relative severity, or extent, of
the disease. The objectives are illustrated in Table 1.
The nature of staging has meant that the data to
support the concept have been largely drawn from
retrospective and observational studies. Much of the
systems development has been through the opinion of
expert panels using these data.
Both the International Union against Cancer (UICC)
and the American Joint Committee on Cancer (AJCC)
published rules on classification and staging which
approval of all national tumour–node–metastasis
(TNM) committees.1,2
Sites in the head and neck region
The TNM classification applies only to carcinomas and
melanomas in the following sites: lip and oral cavity,
pharynx (oropharynx, nasopharynx and hypopharynx),
larynx, maxillary sinus, nasal cavity and ethmoid sinus,
mucosal malignant melanoma, major salivary glands
and thyroid gland. Each site is described having rules
for classification, anatomical sites and subsites where
appropriate, the clinical TNM (cTNM) classification,
the pathological TNM (pTNM) classification, G histo-
pathological grading, stage grouping and a summary.
The main aspects are described here, but specific
details can be found in the most recent UICC and
AJCC TNM booklets.1,2
S54 N ROLAND, G PORTER, B FISH et al.

TABLE I TABLE III

OBJECTIVES OF STAGING HISTOPATHOLOGICAL GRADING SYSTEM FOR
SQUAMOUS CELL CARCINOMA
GX Grade of differentiation cannot be assessed
1. To aid the clinician in the planning of treatment G1 Well differentiated
2. To give some indication of prognosis G2 Moderately differentiated
3. To assist in evaluation of the results of treatment G3 Poorly differentiated
4. To facilitate the exchange of information between treatment G4 Undifferentiated
centres
G = Histopathological grading
5. To contribute to the continuing investigation of human cancer

lower (i.e. less advanced) category should be chosen.

General rules After assigning the cTNM and pTNM categories, the
The TNM system for describing the anatomical extent patient should then be classified in a Stage Group.
of the disease is based on three components (Tables Once established, this must remain unchanged in the
II–IV): medical records.1,2
T – Extent of the primary tumour See site-specific chapters for each detailed tumour
N – Absence or presence and extent of regional classification.
lymph node metastases
M – Absence or presence of distant metastases Histopathological grading
All cases should be confirmed microscopically. Two The histological grading of squamous cell carcinoma
classifications should be documented for each site, represents estimation by the pathologist of the expected
namely: cTNM (clinical (pre-treatment) classification) biologic behaviour of the neoplasm. Although it is
and pTNM (post-surgical histopathological classifica- subject to inter- and intra-observer errors, it has been
tion). The clinical stage is essential to select and evalu- suggested such information in conjunction with other
ate therapy, while the pathological stage provides the characteristics of the primary tumour is useful in the
most precise data to estimate prognosis and calculate rational approach to therapy.3 The grade can be
end results. It should be remembered that if there is applied to all head and neck sites except thyroid.
doubt concerning the correct T, N or M category to
which a particular case should be allotted, then the Additional descriptors
Designation is now applicable when sentinel lymph
node biopsy is attempted using the suffix (sn) after N
TABLE II stage. Optional descriptors for perineural invasion
AN OVERVIEW OF THE TNM STAGING TERMINOLOGY (Pn), lymphatic invasion (L) and venous invasion (V)
may be used.
T – Primary tumour The absence or presence of residual tumour after
TX Primary tumour cannot be
assessed treatment may be described by the symbol R. A recur-
T0 No evidence of primary rent tumour, when classified after a disease-free inter-
Tis
tumour
Carcinoma in situ
val is identified by the prefix ‘r’. The prefix ‘a’
T1, T2, T3, T4 Increasing size and/or indicates that classification is first determined at
local extent of the
primary tumour
N – Regional lymph nodes TABLE IV
NX Regional lymph nodes
cannot be assessed OPTIONAL DESCRIPTORS USED FOR
N0 No evidence of regional HISTOPATHOLOGICAL REPORTING IN
lymph node metastases SQUAMOUS CELL CARCINOMA
N1, N2, N3 Increasing involvement of Optional descriptors
regional lymph nodes
M – Distant metastasis Pn – Perineural invasion
M0 No distant metastasis PnX Perineural invasion cannot be assessed
M1 Distant metastasis Pn0 No perineural invasion
The previously included MX category is now considered to be Pn1 Perineural invasion
inappropriate. L – Lymphatic invasion
The category M1 may be further specified according to the LX Lymphatic invasion cannot be
following notation: assessed
L0 No lymphatic invasion
Pulmonary PUL Bone marrow MAR L1 Lymphatic invasion
Osseous OSS Pleura PLE V – Venous invasion
Hepatic HEP Peritoneum PER VX Venous invasion cannot be assessed
Brain BRA Adrenals ADR V0 No venous invasion
Lymph nodes LYM Skin SKI V1 Microscopic venous invasion
Other OTH V2 Macroscopic venous invasion
ASSESSMENT AND STAGING: UK GUIDELINES S55

autopsy. The suffix ‘m’ is used to indicate the presence TABLE VI

of multiple primary tumours at a single site. In cases STAGE GROUPING FOR CARCINOMA OF THE
where multimodality treatment is used, the cTNM or NASOPHARYNX
pTNM is identified by a ‘y’ prefix which categorises Stage 0 Tis N0 M0
the extent of tumour actually present at the time of Stage I T1 N0 M0
that examination. Stage II T1 N1 M0
T2 N0,N1 M0
The C-factor, or certainty factor, reflects the validity Stage III T1,T2 N2 M0
of classification according to the diagnostic methods T3 N0, N1, N2 M0
employed (C1–C5). C1 would be evidence from stand- Stage IVA T4 N0, N1, N2 M0
Stage IVB Any T N3 M0
ard diagnostic means whereas C5 is evidence from Stage IVC Any T Any N M1
autopsy. Generally speaking, pre-therapeutic clinical
staging of HNCs is equivalent to C1, C2 and C3,
whilst pathological classification is equivalent to C4.1,2 the patient, the duration and severity of symptoms and
signs and the presence and severity of concurrent
Related classifications disease should all be documented.
The World Health Organization (WHO) has developed Computed tomography (CT) and magnetic reson-
a series aimed at classification of tumours. The WHO ance imaging are now established as the mainstay
International Classification of Diseases for Oncology investigations in the pre-operative work-up of patients
(ICD-O) is a coding system for neoplasms by topog- with HNC, to delineate the extent and size of the
raphy and morphology and for indicating behaviour primary tumour, to determine the presence (particular-
(e.g. malignant and benign).4 This coded nomenclature ly when risk of occult nodes is >20 per cent), number
is identical in the morphology field for neoplasms to and position of cervical lymph nodes, to search for an
the Systemised Nomenclature of Medicine.5 It is occult primary and to locate a synchronous primary or
recommended that the WHO classification of tumours distant metastases (particularly the chest). Appropriate
is used for classification and definition of tumour screening for synchronous tumours and distant metasta-
types and that the ICD-O code is used for storage and ses is particularly important in advanced tumours.
retrieval of data. Several studies have suggested that a CT scan should
be obtained in preference to a plain chest X-ray as
Stage grouping this may miss significant lung pathology.6 There is a
After TNM, classification of tumours should be assigned
a stage grouping between 0 or I and IV (Tables V). The
grouping adopted is designed to ensure, as far as pos- TABLE VII
sible, that each group is more or less homogeneous in STAGE GROUPING FOR THYROID CARCINOMA
respect of survival and that the survival rates for each
cancer stage are distinctive. Carcinoma in situ is cate- Papillary or follicular under 45 years
Stage I Any T Any N M0
gorised as stage 0; cases with distant metastasis as Stage II Any T Any N M1
stage IV. The exceptions to this grouping are for carcin- Papillary or follicular 45 years and
oma of the nasopharynx, carcinoma of the thyroid older
Stage I T1a, T1b N0 M0
(Tables VI and VII) and mucosal melanoma.1,2 Stage II T2 N0 M0
Stage III T3 N0 M0
Methods of assessment T1, T2, N1a M0
T3
The aim is to define in each patient all of the factors Stage IVA T1, T2, N1b M0
relevant to the natural history and outcome of the rele- T3
vant disease, thereby enabling a patient with cancer to Stage IVB T4a N0, M0
N1
be grouped with other similar cases. The sex and age of Stage IVC T4b Any N M0
Any T Any N M1
Medullary
TABLE V Stage I T1a, T1b N0 M0
Stage II T2, T3 N0 M0
STAGE GROUPING FOR HEAD AND NECK CANCERS
Stage III T1, T2, N1a M0
EXCLUDING NASOPHARYNX, THYROID AND
T3
MUCOSAL MELANOMA
Stage IVA T1, T2, N1b M0
Stage 0 Tis N0 M0 T3
Stage I T1 N0 M0 Stage IVB T4a Any N M0
Stage II T2 N0 M0 Stage IVC T4b Any N M0
Stage III T1, T2, T3 N1 M0 Any T Any N M1
T3 N0 M0 Anaplastic (all cases are stage IV)
Stage IVA T1, T2, T3 N2 M0 Stage IVA T4a Any N M0
T4a N0, N1, N2 M0 Stage IVB T4b Any N M0
Stage IVB Any T N3 M0 Stage IVC Any T Any N M1
T4b Any N M0
Separate stage groupings are recommended for papillary and fol-
Stage IVC Any T Any N M1
licular, medullary and undifferentiated carcinomas
S56
growing body of evidence that points to the value of 18F
fluoro-deoxyglucose-positron emission tomography/
CT in the management of HNC patients and predicting
patient-related outcomes. It is invaluable in the detec-
tion of the unknown primary and useful in the confirm-
ation of residual or recurrent disease, but is not
routinely used in initial staging assessment.7
Endoscopy and biopsy should be performed by a
senior surgeon and in all cases by the head and neck
surgeon responsible for any future procedure. This
should include for each tumour a description, diagram-
matic representation and preferably also photographic
documentation. Routine panendoscopy (oesophago-
scopy and bronchoscopy) is contentious. Proponents
point out that these procedures require very little
time, and may be performed easily during planned,
direct laryngoscopy. A large meta-analysis found a
small advantage to panendoscopy in detection of
second primary tumours during analysis of multiple
prospective studies.8 Opponents point out that the
appropriate use of symptom directed investigations in
addition to routine chest radiography have a similar
detection rate compared with screening endoscopy
and avoid unnecessary risk and expense in asymptom-
atic patients.9 McGarey et al.10 concluded that while
rigid oesophagoscopy is safe, the utility is low for
cancer staging and for detection of non-malignant
oesophageal disease. Review of the literature and ana-
lysis of a large national cancer dataset indicate that the
incidence of synchronous oesophageal malignant neo-
plasms in patients with head and neck squamous cell
carcinoma is low and has been decreasing during the
past three decades.10 Thus, screening oesophagoscopy
should be limited to patients with head and neck squa-
mous cell carcinoma who are at high risk for synchron-
ous oesophageal malignant neoplasms.
There is a natural desire to confer a stage on the
tumour at presentation in the clinic and certainly after
endoscopy. This should be avoided. It is better to rely
on descriptive text to avoid changing the stage as
more information becomes available. The clinical
(pre-treatment) classification (cTNM) based on exam-
ination, imaging, endoscopy and biopsy should be
clearly documented in the case-file only when all of
the above information is collated. The UICC book
should be available in every theatre and clinic to
assist in applying the correct stage.
Regional lymph nodes
The status of the regional lymph nodes in HNC is of
such prognostic importance that they must be assessed
for each patient and tumour. Lymph nodes are
described as ipsilateral, bilateral, contralateral or
midline; they may be single or multiple and are mea-
sured by size, number and anatomical location
(Table VIII). Midline nodes are considered ipsilateral
nodes except in the thyroid. Direct extension of the
primary tumour into lymph nodes is classified as
lymph node metastasis.1,2
N ROLAND, G PORTER, B FISH et al.
TABLE VIII
N STAGING FOR REGIONAL LYMPH NODES
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node. 3 cm or less in
greatest dimension
N2 N2a Metastasis in a single ipsilateral lymph node, more
than 3 cm but not more than 6 cm in greatest dimension
N2b Metastasis in multiple ipsilateral lymph nodes, none
more than 6 cm in greatest dimension
N2c Metastasis in bilateral or contralateral lymph nodes,
none more than 6 cm in greatest dimension
N3 Metastasis in a lymph node more than 6 cm in greatest
dimension
Imaging for node detection and delineation is recom-
mended in the following settings: the neck is being
scanned as part of the evaluation of the primary
tumour; there is a high chance of occult disease (e.g.
supraglottic primary); to assess the extent of nodal
disease; to define any deep nodal fixation; or if clinical
assessment is difficult because of a short, fat or previ-
ously irradiated neck.
Lymph nodes are subdivided into specific anatomic
sites and grouped into seven levels for ease of descrip-
tion. The pattern of lymphatic drainage varies for dif-
ferent anatomic sites. However, the location of the
lymph node metastases has prognostic significance.
Survival is significantly worse when metastases
involve lymph nodes beyond the first echelon of
lymphatic drainage.11 It is particularly poor for
lymph nodes in the lower regions of the neck, i.e.
levels IV and V (supraclavicular area).
International Union Against Cancer and AJCC rec-
ommend that each N-staging category be recorded to
show, in addition to the established parameters,
whether the nodes involved are located in the upper
(U) or lower (L) regions of the neck, depending on
their location above or below the lower border of the
thyroid cartilage.1,2
The definitions of the N categories for all head and
neck sites are the same (Table VIII) except thyroid
(Table IX) and nasopharynx (Table X). The natural
history and response to treatment of cervical nodal
metastases from nasopharynx are different, in terms
of their impact on prognosis, so they justify a different
N classification. Regional lymph node metastases from
well-differentiated thyroid cancer do not significantly
TABLE IX
N STAGING FOR THYROID CARCINOMA
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
N1a Metastasis in level VI (pre-tracheal, pre-laryngeal,
paralaryngeal) nodes
N1b Metastasis in other unilateral, bilateral or contralateral
cervical or retropharyngeal or superior mediastinal
lymph node(s)
ASSESSMENT AND STAGING: UK GUIDELINES
TABLE X
N STAGING FOR NASOPHARYNX
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Unilateral cervical, unilateral or bilateral retropharyngeal
lymph node(s), 6 cm or less in greatest dimension,
above supraclavicular fossa
N2 Bilateral cervical lymph node(s), 6 cm or less in greatest
dimension, above supraclavicular fossa
N3 Metastasis in lymph node >6 cm and/or (in the
supraclavicular fossa:
(N3a) Greater than 6 cm in dimension
(N3b) In the supraclavicular fossa
Note: Midline nodes are considered ipsilateral nodes, and the
supraclavicular triangle is defined by the lines joining the follow-
ing three points – the superior margin of the clavicle at its sternal
and acromial ends, and the point where the line of the neck meets
the shoulder.
affect the ultimate prognosis and therefore also justify a
unique system.
Pathological classification (pTNM)
The pT, pN and pM categories correspond to the T, N
and M categories, respectively. The extent of
the tumour in terms of the location and level of the
lymph node should be documented. In addition, the
number of nodes that contain tumour and the presence
or absence of extracapsular spread of the tumour should
be recorded. Histological examination of a selective
neck dissection including central compartment speci-
men usually includes six or more lymph nodes; a
radical or modified radical neck dissection specimen
includes 10 or more lymph nodes.1,2
The current TNM system relies on morphology of
the tumour (anatomical site and extent of disease)
with little or no attention given to patient factors.
However, the literature does suggest that symptom
severity12 and comorbidity13 have a significant
impact on outcomes. It is therefore recommended that
these data be recorded. Definitions of TNM categories
may be altered or expanded for clinical or research pur-
poses as long as the basic definitions are recorded and
not changed. Despite the obvious value of staging, both
in the management of individual patients and for the
grouping of patients in trials and reports of treatment,
it does have its limitations. The most insidious of
these is that attempts to increase the accuracy of
staging leads to greater complexity, and hence paradox-
ically to more errors and an increased likelihood of
non-compliance by the person responsible for
staging. Advances in methods of collecting and record-
ing data will hopefully reduce these errors. Changes in
the TNM classification should and will only occur,
based on the appropriate collection, presentation and
analysis of data, in the forum of the UICC and
AJCC.3,4 The principles, practice and limitations of
the current staging system are well documented in
many major texts.14–16 Changes between editions
tend to be conservative and commentaries regarding
S57
HNC reflect this.17 It is seven years since the 7th
edition of the UICC and AJCC staging manuals and
the updated version is eagerly awaited. The early indi-
cations are that changes will be only subtle and few.
Key points
• Staging of head and neck cancer is a system
designed to express the relative severity, or
extent, of the disease. It is meant to facilitate an
estimation of prognosis and provide useful infor-
mation for treatment decisions. Classification by
anatomical extent of head and neck cancer as
determined clinically and histopathologically is
the TNM System
• Radiological investigations to evaluate the
primary site should be performed prior to biopsy
to avoid the effect of upstaging from the oedema
caused by biopsy trauma
• The sex and age of the patient, the duration and
severity of symptoms and signs, and the presence
and severity of inter-current disease should all be
documented
• Assessment by endoscopy and biopsy should be
performed by a senior surgeon and in all cases
by the Head & Neck surgeon responsible for any
future procedure
• The clinical (pre-treatment) classification (cTNM)
based on examination, imaging, endoscopy and
biopsy should be clearly documented in the
case-file only when all the information is collated
• Individual TNM classifications should be
assembled into four groups – stage groups
(stages I–IV), each with similar survival outcomes
• The UICC book should be available in every
theatre, MDT meeting and clinic to assist in apply-
ing the correct stage.
References
1 Sobin LH, Wittekind CH, Gospodarowicz M. TNM
Classification of Malignant Tumours, UICC, 7th edn.
New York: Wiley-Liss, 2009
2 Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti
A, eds. The AJCC Cancer Staging Manual, 7th edn. New York:
Springer, 2009
3 Roland NJ, Caslin AW, Nash J, Stell PM. The value of grading
squamous cell carcinoma of the head and neck. Head Neck
1992;14:224–9
4 Fritz A, Percy C, Jack A, Shanmugaratnam K, Sobin L, Parkin
DM et al., eds. WHO International Classification of Diseases
for Oncology ICD-O, 3rd edn. Geneva: WHO, 2000
5 SNOMED International: The Systemised Nomenclature of
Human and Veterinary Medicine. Northfield, Ill: College of
American Pathologists, SNOMED CT. The Systematized
Nomenclature of Medicine Clinical Terms. Copenhagen
Denmark. The International Health Terminology Standards
Development Organisation, http://www.ihtsdo.org/snomed-ct
(accessed 27 April 2016)
6 Ghosh SK, Roland NJ, Kumar A, Tandon S, Lancaster JL,
Jackson SR et al. Detection of synchronous lung tumors in
patients presenting with squamous cell carcinoma of the head
and neck Head Neck 2009;31:1563–70
7 Sheikhbahaei S1, Marcus C1, Subramaniam RM. 18F FDG
PET/CT and head and neck cancer: patient management and
outcomes. PET Clin 2015;10:125–45
S58
8 Haughey BH, Gates GA, Arfken CL, Harvey J. Meta analysis of
second malignant tumours in head and neck cancer: the case for
an endoscopic screening protocol. Ann Otol Rhinol Laryngol.
1992;101:105–12
9 Davidson J, Witterick I, Gilbert R, Brown D, Birt D, Freeman
J et al. The role of panendoscopy in the management
of mucosal head and neck malignancy. Head Neck 1999;22:
1–6
10 McGarey PO Jr, O’Rourke AK, Owen SR, Shonka DC Jr, Reibel
JF, Levine PA et al. Rigid esophagoscopy for head and neck
cancer staging and the incidence of synchronous esophageal
malignant neoplasms. JAMA Otolaryngol Head Neck Surg
2016;142:40–5
11 Jones AS, Roland NJ, Field JK, Phillips D. The level of cervical
lymph node metastases: their prognostic relevance and relation-
ship with head and neck squamous carcinoma primary sites.
Clin Otolaryngol 1994;19:63–9
12 Pugliano FA, Picirillo JF, Zequeria MR, Fredrickson JM, Perez
CA, Simpson JR et al. Symptoms as an index of biologic behav-
iour in head and neck cancer. Otolaryngol Head Neck Surg
1999;120:380–6
N ROLAND, G PORTER, B FISH et al.
13 Picirillo JF. Importance of comorbidity in head and neck cancer.
Laryngoscope 2000;110:593–602
14 Roland NJ. Staging of Head and Neck Cancer. Scott-Brown’s
otolaryngology, Head and Neck Surgery, Volume 2. 7th edn.
London: Hodder Arnold, 2008;2359–71
15 Roland NJ. Assessment of Head and Neck Cancer. Stell & Maran’s
Head and Neck Surgery, 5th edn. London: Hodder Arnold, 2010
16 Gospodarowicz M, O’Sullivan B, Sobin L. Prognostic Factors
in Cancer, 4th edn. New York: Wiley-Liss, 2009
17 Paleri V, Mehanna H, Wight RG. TNM classification of malig-
nant tumours 7th edn: what’s new for head and neck? Clin
Otolaryngol. 2010;35:270–2
Address for correspondence:
Nick Roland,
Department of ENT – Head & Neck Surgery,
University Hospital
Aintree,
Liverpool, UK
E-mail: DrNJRoland@aol.com
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S59–S65. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000451

Pathological aspects of the assessment of head

and neck cancers: United Kingdom National
Multidisciplinary Guidelines

T R HELLIWELL1, T E GILES2
1
Department of Cellular Pathology, Liverpool Clinical Laboratories, University of Liverpool, and 2Department of
Cellular Pathology, Liverpool Clinical Laboratories, Liverpool, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. It introduces the current best practice in histopathology and cytopathology as it pertains to
head and neck and thyroid cancers.
Recommendations
• Accurate diagnosis of the type of malignancy is a key component of effective management. (R)
• Surgeons and oncologists should understand the scope and limitations of cellular pathology in order to inform
multidisciplinary discussions. (R)
• A clinically suspected diagnosis of malignancy should be confirmed by biopsy or cytology before operation. (R)
• Cytopathological diagnoses should be discussed with surgeons and radiologists to maximise the information
gained from each modality of investigation. (R)
• Pathological investigations are the basis for accurate cancer staging and stratification of clinical outcomes. (R)

Introduction surgical excision margins when there is clinical doubt

This paper is an overview of the use of laboratory
investigations and focuses on the important elements
of cancer pathology reports that clinicians should use
when discussing the implications of a diagnosis and
management options with patients and with colleagues
in a multidisciplinary setting. The recommendations for
pathology practice are based on published evidence; key
references are provided in the World Health Organisation
(WHO) Classification of Tumours1 and in the series of
Histopathology Datasets published by the Royal
College of Pathologists.2,3 Pathologists have critically
important roles in confirming or excluding specific dis-
eases on the basis of cytology or diagnostic biopsy, in
assessing the adequacy of treatment, recognising key pre-
dictive and prognostic factors, and in contributing evi-
dence-based criteria for the appropriate stratification of
clinical outcomes.
Use of cellular pathology services
Frozen section
Patient management should be guided primarily by pre-
operative biopsy and/or fine needle aspiration (FNA)
cytology. Intra-operative frozen sections have a limited
role and are appropriately used for the assessment of
as to adequacy.4 Frozen sections are occasionally used
to confirm the diagnosis of branchial cleft cysts in
older people, of papillary, medullary or anaplastic
thyroid carcinomas5 or to identify lymph node involve-
ment in thyroid cancers; they should not be used to dif-
ferentiate follicular thyroid carcinoma from adenoma or
follicular variant papillary carcinoma. It should be
appreciated that the quality of frozen sections is not as
good as paraffin sections and that important information
may be missed or destroyed through inappropriate use of
frozen sections, particularly if small pieces of tissue are
submitted for examination.
Definitive operative specimen
Specimens should be submitted in an adequate
amount of 10 per cent neutral buffered formalin (at
least three times the volume of the specimen) unless
there is prior agreement with the laboratory.2 The
site and nature of each specimen should be clearly
described on the request form and should be appropri-
ately orientated. The form must include the clinical
indication for the operation, the duration of signs
and symptoms, pre-operative radiotherapy (RT) or
chemotherapy, and details of previous biopsies or
S60
cytological investigations, and relevant biochemistry
(particularly for thyroid diseases).
Lymph node specimens
The site of origin of lymph nodes should be recorded,
and formal neck dissections should clearly state which
nodal groups are included and should be clearly orien-
tated, preferably with a diagram.6 The optimal handling
of biopsies for suspected lymphoma should be dis-
cussed with the laboratory; it is often useful to collect
fresh tissue in a transport medium for possible cytogen-
etic and molecular studies.
The predictive value of sentinel node biopsy is now
recognised and is becoming established practice, particu-
larly for the early-stage oral carcinoma.7 The pathologic-
al assessment of sentinel nodes is highly demanding of
laboratory time and expertise, involving multiple sections
and immunocytochemistry.8 This should only be under-
taken if appropriately resourced.
Resection specimens including bone
When cancer resection specimens contain bone, it is
often possible to obtain a preliminary report on the
soft tissue components of the specimen while the
bone is decalcified before processing the tissues to
assess the extent of bone invasion and bony margins.
Decalcification may take several days or weeks
depending on the density of the bone.
Immunocytochemistry and molecular pathology
Immunocytochemistry plays an important role in the
correct diagnosis of primary head and neck cancers,
particularly for the less common entities. The prognos-
tic value of assessing oropharyngeal carcinomas for
evidence of human papilloma virus infection (HPV)
is established, with current guidance recommending a
combination of immunocytochemistry for p16 protein
overexpression and in situ hybridisation for high-risk
HPV DNA. Morphologically similar poorly differentiated
carcinomas arising in the oropharynx and nasopharynx,
and their nodal metastases may be distinguished by
the presence of HPV and Epstein–Barr virus DNA,
respectively.
In patients with metastatic malignancy in cervical
lymph nodes without evidence of primary disease,
the morphological features of the metastatic tumour
may be useful, e.g. thyroid and salivary neoplasms.
Immunocytochemical investigation of FNA or biopsy
material does not reliably distinguish between primary
sites of squamous cell carcinomas (SCCs) but may be
helpful in identifying adenocarcinomas arising in
the gastrointestinal tract, lungs or prostate. Clinicians
should note that immunocytochemical markers are very
rarely specific for particular tissues and that opinions on
likely primary sites are based on the assessment of a
panel of different markers and the balance of probabil-
ities. Clinical features, such as the pattern of nodal
T R HELLIWELL, T E GILES
disease, and imaging studies should be incorporated
into the multidisciplinary assessment of these patients.
Molecular genetic profiling of head and neck cancers
is not currently recommended outside the research
setting.2,9,10
Multidisciplinary team working
Cellular pathologists are core members of cancer MDTs
and are essential to the provision of a successful service.
The MDT should have a risk-based approach to devel-
oping its policy on pathology review, particularly for
patients who have had diagnostic biopsies in other hos-
pitals. Pathological review is essential for thyroid
cancers and is good practice for other situations.
Malignancies of the upper
aerodigestive tract
Squamous cell carcinoma
The initial diagnosis may be obvious clinically on the
basis of an irregularly infiltrating mass with ulceration,
but should always be confirmed by biopsy as some
inflammatory diseases, e.g. tuberculosis and sarcoidosis,
can mimic carcinomas clinically and other mucosal
malignancies, e.g. lymphoma, may require consideration
of other treatment options. Practical problems that may
preclude definitive diagnosis on diagnostic biopsies
include poor orientation, necrotic or inflammatory
debris, small samples containing few cells and crush
artefact. The edges of laser resection specimens often
show thermal artefacts, making detailed interpretation
impossible. Patients who have been treated with RT
and/or chemotherapy may have biopsies or resections
to assess any residual or recurrent disease at primary
or nodal sites. Extensive scarring, radiation-associated
nuclear atypia and loss of the normal anatomical land-
marks may make assessment of these specimens diffi-
cult. A good chemotherapeutic response may leave a
mass of necrotic tissue containing degenerate keratino-
cytes; viable carcinoma may not be identified even
after extensive histological sampling.
Morphological variants of SCC. Some variants of SCC
are associated with particular difficulties in diagnosis
and clinical assessment but should be managed, stage
for stage, in line with classical carcinomas.
Papillary SCC is typified by an exophytic growth
pattern with fronds of fibrovascular tissue covered by
squamous epithelium showing in situ carcinoma; areas
of invasive carcinoma are often small and limited in
extent. Diagnostic biopsies may show only in situ car-
cinoma despite a bulky tumour. The prognosis is rela-
tively good due to the limited invasive component.
Verrucous SCC has an exophytic growth and is
formed by extremely well-differentiated squamous epi-
thelium with minimal atypia and abundant surface
keratin. Diagnostic biopsies may not show invasion
and the minimal cellular atypia makes pathologists
PATHOLOGICAL ASPECTS OF THE ASSESSMENT OF HEAD AND NECK CANCERS: UK GUIDELINES
reluctant to diagnose malignancy. Repeated biopsies and
appreciation of the discrepancy between a clinically
obvious carcinoma and minimal microscopic atypia are
often needed to make a diagnosis of carcinoma.
Spindle cell carcinomas typically present as polypoid
tumours with an ulcerated surface and are formed by
sheets of atypical spindle cells, often raising the possibil-
ity of sarcoma. Sarcomas of mucosal origin are extremely
rare in adults, but a definitive diagnosis of spindle cell car-
cinoma may only be possible on resection specimens
when small areas of in situ or more typical invasive car-
cinoma are identified. Immunohistochemistry only iden-
tifies squamous epithelial differentiation in about 60–70
per cent of cases.
Oropharyngeal SCCs are usually related to high-risk
HPV infection. Typical HPV-associated carcinomas
are non-keratinising (basaloid) carcinomas, but may
be of any histological type.
Information that should be provided in histopathology
reports. The information available from diagnostic
biopsies is limited but should normally include
whether any carcinoma is invasive or in situ and, for
invasive carcinomas, should provide a provisional esti-
mate of the degree of differentiation and the growth
pattern. In the oral cavity, the depth of invasion or
tissues involved (mucosa, muscle) may guide the
extent of surgery.
Resection specimens provide sufficient tissue to
describe the full range of prognostic information2,11
(Box I); the basis in evidence for this information is
provided in guidelines published by the Royal
College of Pathologists and varies between anatomical
sites.
BOX I
PROGNOSTIC INFORMATION DERIVED FROM
PRIMARY CARCINOMAS
Site and subsite
Histological type of carcinoma
Grade of differentiation
Growth pattern
Maximum diameter
Maximum depth of invasion
Invasion of lymphatic or blood vessels
Invasion of the peri-neural space of nerve trunks
Invasion of bone or cartilage
Distance of carcinoma from resection margins
Dysplasia and intra-epithelial neoplasia
Squamous cell carcinomas are the result of a combin-
ation of genetic mutations, some of which are manifest
in precursor lesions by atypia of the epithelial cells
collectively referred to as dysplasia or intra-epithelial
neoplasia. Severe cytological atypia is associated
with a high risk of progression to carcinoma and,
S61
TABLE I
GRADING SYSTEMS FOR PRECURSOR LESIONS OF
SQUAMOUS EPITHELIAL MALIGNANCIES
WHO Squamous Ljubljana
Classification intraepithelial classification;
2005 neoplasia (SIN) squamous
intraepithelial lesions
(SILs)
Squamous cell Simple hyperplasia
hyperplasia
Mild dysplasia SIN 1 Basal/parabasal cell
hyperplasia
Moderate SIN 2 Low grade SIL
dysplasia
Severe dysplasia SIN 3 High grade SIL
Carcinoma in SIN3 Carcinoma in situ
situ
Note: The categories in the different systems are not strictly com-
parable as different morphological and architectural criteria are
used
in resection specimens, its presence at resection
margins may predict local recurrence. The various,
commonly used, grading systems are summarised in
Table I and, although different criteria are used, each
seeks to place a particular abnormality in a continuous
spectrum of appearances from mild to severe atypia.
There is no UK consensus12 on which grading
system should be recommended, although a majority
of pathologists probably use the WHO dysplasia
system but regard severe dysplasia and in situ carcin-
oma as indistinguishable. A proposed consensus
system for laryngeal lesions based on the Ljubljana
classification13 is gaining recognition, but its transla-
tion to UK practice is limited. Management decisions
should take account of the microscopic severity of the
lesion and its clinically assessed extent.
Other mucosal malignancies
Adenocarcinomas. This may be of surface or salivary
type. Those derived from surface epithelium of the
nose and sinuses may resemble intestinal carcinomas
and have a relatively poor prognosis compared with
other low grade adenocarcinomas.
Sinonasal undifferentiated (anaplastic) carcinoma. This
is a rare, clinically aggressive neoplasm composed of
cells that are undifferentiated on routine stains but
which show varying degrees of neuroendocrine differ-
entiation on immunocytochemistry. These carcinomas
often result in bone destruction and extension into the
orbit or cranial cavity and have a poor prognosis
despite aggressive surgery and chemoradiotherapy.
Olfactory neuroblastoma (esthesioneuroblastoma). This
presents as a polypoid mass high in the nasal cavity.
The histological features are characteristic and immuno-
cytochemistry is positive for neuroendocrine markers.
Morphological grading systems are of limited prognos-
tic value. Despite spread to regional nodes and more
S62
distant sites, prognosis is good with a 78 per cent five-
year survival after surgery and RT.
Malignant melanoma. This most often arises in the nasal
cavities and less often in the sinuses, presenting in
adults over 50 years as polypoid, friable haemorrhagic
masses. Histologically there is a wide range of appear-
ances with very variable melanin production (30 per
cent are amelanotic). Survival is poor with death due
to widespread metastasis and/or extensive local
recurrence.
Lymphomas. This may present as primary mucosal
malignancies in the sinonasal tract and tonsils. Almost
all are non-Hodgkin’s lymphomas with natural killer/
T-cell lymphomas mainly affecting the sinonasal tract
and B-cell lymphomas arising in the tonsils.
Nasopharyngeal carcinoma. This includes keratinising
SCCs and non-keratinising differentiated and undifferen-
tiated carcinomas and is usually related to Epstein–Barr
virus infection. The synonym of ‘lymphoepithelioma’
should not be used. Keratinising carcinomas are more
radioresistant than non-keratinising and undifferentiated
carcinomas.
Diagnosis and management of neck lumps
Fine needle aspiration
Fine needle aspiration (FNA) of tissue by a well-trained
operator is an essential part of the diagnostic assessment
of patients with neck or thyroid lumps and as part of
staging procedures for patients with the known head
and neck cancer.14,15 High-quality preparations are
essential for an effective service. Either rapidly air-
dried slides or needle washings into preservative
solution may be required depending on the clinical cir-
cumstance. The cytological diagnosis of metastatic
SCC in cervical nodes is usually straightforward, but
cystic metastases can be difficult to distinguish from
benign cystic lesions containing squamous cells such
as branchial cleft cysts; a high degree of clinical suspi-
cion for malignancy is required in older patients with
cystic lesions containing squamous cells. Haemorrhage
into cystic neck nodes may conceal underlying malig-
nancy, particularly metastatic papillary carcinoma from
the thyroid. Multidisciplinary correlation of findings is
of fundamental importance.
FNA cytology is the method of choice for monitor-
ing patients known to have lymphoma as cytology
can document disease recurrence and can indicate
transformation from low to high grade disease. The
primary diagnosis of lymphoma can be made from
FNA specimens if the laboratory repertoire includes
molecular techniques and flow cytometry. FNA
cytology is an effective method to triage patients into
those in whom significant disease can be excluded,
those in whom a definitive diagnosis of benign
disease or metastatic malignancy can be made, and
those with possible lymphoma who need lymph node
T R HELLIWELL, T E GILES
biopsy. Where malignancy is identified, additional
immunocytochemical and molecular testing for planning
management is possible with appropriate specimen col-
lection procedures.
Neck dissections
The presence or absence of nodal metastasis is a key com-
ponent of tumour–node–metastasis (TNM)16 staging and
determines further management. The pathological assess-
ment of nodes in resection specimens verifies pre-opera-
tive imaging studies and identifies small volume nodal
disease that is beyond the resolution of current imaging
techniques.
The terminology of possible nodal involvement by
carcinoma includes:
• Isolated tumour cells (ITCs) – collections of cells
<0.2 mm diameter
• Micrometastasis – tumour deposits 0.2–2 mm in
diameter
• Conventional metastasis – a tumour deposit more
than 2 mm diameter
• Extracapsular spread – carcinoma extending
through a breach in the capsule from a lymph
node into surrounding connective tissue.
For TNM staging, the presence of ITCs is classified as
pN0 as their significance is unknown. Micrometastases
are recorded as pN1(mi), pN2b(mi) or pN2C according
to their extent in multiple nodes. Core pathological data
for nodal metastases are shown in Box II.
BOX II
PROGNOSTIC INFORMATION DERIVED FROM
LYMPH NODE EXCISIONS
Number of positive nodes
Sites of positive nodes
Size of largest metastasis
Presence or absence of extracapsular spread
Salivary neoplasms
Most tumours arising in the major or minor salivary
glands are benign (although the proportions vary from
site to site), but pre-operative suspicion of malignancy
may be raised on clinical examination, from imaging
studies or from pre-operative FNA cytology. All
tumours of the major salivary glands should have pre-
operative FNA cytology to guide treatment, which can
usually accurately diagnose pleomorphic salivary
adenoma and Warthin’s tumour with confidence, differ-
entiate benign neoplasms from malignant in 81–98 per
cent of cases, but which is less good at establishing a
specific type of carcinoma. The main categories of
salivary carcinoma are well defined, but these tumours
have many morphological variants and precise histo-
logical diagnosis often requires a specialist opinion.
PATHOLOGICAL ASPECTS OF THE ASSESSMENT OF HEAD AND NECK CANCERS: UK GUIDELINES S63

Many salivary neoplasms have characteristic genetic TABLE II

translocations17 which aid diagnosis and may lead to CATEGORISATION OF THYROID FNAS WITH
targeted therapeutics. The core pathological data from LIKELIHOOD OF MALIGNANCY (LOM) (RCPATH AND
salivary resections for neoplasia are shown in Box III. BSCC GUIDELINES)
Thy 1 Non-diagnostic for cytological LOM 0–10%
diagnosis
Thy 1c Non-diagnostic for cytological
BOX III diagnosis – cystic lesion
PROGNOSTIC INFORMATION DERIVED FROM Thy 2 Non-neoplastic LOM 0–3%
SALIVARY GLAND RESECTIONS Thy 2c Non-neoplastic, cystic lesion
Thy 3a Neoplasm possible – atypia/non- LOM 5–15%
The histological type of neoplasm diagnostic
(according to the WHO Classification) Thy 3f Neoplasm possible, suggesting LOM 15–30%
follicular neoplasm
The grade of malignancy (see text) Thy 4 Suspicious of malignancy LOM 60–75%
The distance to the resection margins Thy 5 Malignant LOM 97–100%
The presence or absence of peri-neural or vascular
invasion
staging16 (Box IV). Some histological variants of
The presence or absence of lymph node
thyroid carcinomas have prognostic importance. For
involvement
diagnostic purposes, oncocytic (Hürthle cell) follicular
tumours are regarded as a variant of follicular tumours
and the criteria for malignancy are the same. The pres-
Grading of the degree of malignancy is prognostically
ence of any poorly differentiated or anaplastic compo-
useful for some salivary carcinomas. Grading of
nent affects prognosis.3
mucoepidermoid carcinomas relates to metastatic
potential and survival, whichever grading system is
used. Acinic cell carcinomas are usually circumscribed
BOX IV
but incompletely encapsulated; grading on the basis of PROGNOSTIC DATA FROM THYROID
cytological features is not generally useful, except for RESECTION SPECIMENS
rare tumours showing dedifferentiation. Assessment
of Ki-67 (MIB1) labelling is of prognostic value, and Histological type of malignancy
acinic cell carcinomas with indices of >5 per cent Whether carcinoma is unifocal or multifocal
behaving more aggressively. The growth pattern of Maximum dimension of carcinoma (largest if
adenoid cystic carcinoma is related to metastatic poten- multifocal)
tial, with 0–4 per cent of cribriform, hyaline and Closest distance to surgical resection margin
tubular carcinomas, and 33 per cent of solid (basaloid) (R status)
carcinomas metastasising to local lymph nodes. Distant Extension into extrathyroidal tissues (macroscopic
metastasis is more common in solid tumours. Salivary or microscopic)
duct carcinoma is a high-grade malignancy morpho- Presence of lymphatic or vascular invasion
logically resembling ductal carcinoma of the breast. Site and number of lymph nodes sampled and those
About 70 per cent express androgen receptors and involved
15 per cent express HER-2 (human epithelial growth
factor receptor 2); features which may influence
therapy. Carcinomas arising in pleomorphic adenomas Papillary carcinoma
may be of any or mixed histological type; the extent of
invasion is prognostically useful as invasion more than A single papillary microcarcinoma (≤10 mm diameter)
5–6 mm from the capsule of the residual adenoma is discovered incidentally in a resection performed for
associated with a high risk of local recurrence and another disease is not thought to have a significant
distant metastasis. Non-invasive or minimally invasive risk of recurrence or metastasis. Some microcarcino-
carcinomas ex pleomorphic adenoma are true malig- mas are potentially more aggressive including those
nancies, but have a very low rate of disease progression. with multifocal disease, extrathyroid extension and
lymphatic invasion.
Tall cell and columnar variants of papillary carcin-
Thyroid cancers oma may be more aggressive, while the outcome of
Most lesions will have had FNA before surgery. the diffuse sclerosing variant is a matter of debate.
Immediate assessment of the adequacy of aspirates Diagnosis of the follicular variant of papillary car-
may be helpful. The descriptive cytology report cinoma (FVPC) may be difficult and require specialist
informs clinical decisions on management and should opinion. The non-encapsulated invasive FVPC has a
incorporate a categorical summary3,18 (Table II). metastatic potential similar to that of classical papillary
For all malignant thyroid tumours, the national carcinoma, while encapsulated FVPC has metastatic
dataset for histopathology reports3 defines core data potential related to the number of foci of vascular
items of prognosis importance that will allow TNM invasion.
S64
Follicular carcinoma
A follicular neoplasm is defined as carcinoma on the
basis of capsular and/or vascular invasion. Minimally
invasive follicular carcinomas show only focal micro-
scopic vascular and/or capsular invasion. Tumours
showing only capsular invasion have a minimal risk of
metastasis. The risk of metastasis increases with vascular
invasion, but no significance is attached to the number of
foci of vascular invasion. Widely invasive follicular car-
cinoma shows obvious gross invasion or extensive
microscopic infiltration of thyroid parenchyma, vessels
or extrathyroidal tissues. The number of foci of vascular
invasion should be described but is not prognostically
significant.
Medullary carcinoma
The diagnosis should be confirmed by calcitonin
immunoreactivity, although some poorly differentiated
carcinomas only express carcinoembryonic antigen
(CEA). Although there are variations in the cellular
pattern and presence of amyloid these are unimportant
prognostically compared with the tumour stage and
completeness of excision. In the syndromes of multiple
endocrine neoplasia type 2 and familial medullary
thyroid carcinoma, medullary carcinoma is often multi-
focal and preceded and/or accompanied by C-cell
hyperplasia. Genetic testing for RET mutations will
detect familial syndromes.
Poorly differentiated carcinoma
This group is defined as follicular or papillary carcin-
oma with necrosis and/or a mitotic count of five or
more in ten high-power microscopic fields. The
growth pattern may be insular, trabecular or solid.
Poorly differentiated carcinomas have a poorer progno-
sis than differentiated carcinomas with variable
response to radio-iodine treatment.
Undifferentiated/anaplastic carcinoma
Anaplastic carcinoma is diagnosed where a follicular or
papillary carcinoma shows even a minor undifferenti-
ated (anaplastic) component. Most undifferentiated
tumours will be diagnosed by FNA cytology, core or
open biopsy and will not have a surgical resection.
The report should describe how immunocytochemistry
has been used to exclude other poorly differentiated
malignancies, especially lymphoma.
Lymphoma
The diagnosis of thyroid lymphoma is usually made on
core or open biopsy rather than resection specimens
and may require extensive immunocytochemical and
molecular testing. It is important to distinguish
between primary thyroid lymphoma and involvement
of the thyroid by lymphoma as part of a wider disease.
T R HELLIWELL, T E GILES
Recommendations
• Accurate diagnosis of the type of malignancy
is a key component of effective management
(R).
• Surgeons and oncologists should understand
the scope and limitations of cellular pathology
in order to inform multidisciplinary
discussions (R)
• A clinically suspected diagnosis of malignancy
should be confirmed by biopsy or cytology
before operation (R)
• Cytopathological diagnoses should be
discussed with surgeons and radiologists to
maximise the information gained from each
modality of investigation (R)
• Pathological investigations are the basis for
accurate cancer staging and stratification of
clinical outcomes (R)
Acknowledgements
The authors acknowledge the contributions of Julia
A. Woolgar, Roderick H.W. Simpson and Timothy J
Stephenson to the previous edition of this paper.
References
1 Barnes L, Eveson JW, Reichart P, Sidransky D. Pathology and
Genetics of Head and Neck Tumours. World Health
Organisation Classification of Tumours. Lyon, France: IARC
Press, 2005
2 Helliwell TR, Woolgar JA. Datasets for Histopathology Reports
on Head and Neck and Salivary Cancers. London: Royal
College of Pathologists, 2013
3 Stephenson T, Johnson S. Dataset for Thyroid Cancer
Histopathology Reports. London: Royal College of Pathologists,
2014
4 Thompson LDR. Intraoperative consultation and grossing tech-
niques. In: Thompson LDR, ed. Endocrine Pathology.
Philadelphia: Elsevier, 2006;351–7
5 Osamura RY, Hunt JL. Current practices in performing frozen
sections for thyroid and parathyroid pathology. Virchows
Archiv 2008;453:433–40
6 Woolgar JA, Triantafyllou A. Lymph node metastases in head
and neck malignancies: assessment in practice and prognostic
importance. Diag Histopathol 2010;16:265–75
7 Schilling C, Stoeckli SJ, Haerle SK, Broglie MA, Huber GF,
Sorensen JA. Sentinel European Node Trial (SENT): 3-year
results of sentinel node biopsy in oral cancer. Eur J Ca 2015;
51:2777–84
8 Den Toom IJ, Heuveling DA, Flach GB, van Weert S,
Karagozoglu KH, van Schie A et al. Sentinel node biopsy for
early-stage oral cavity cancer: the VU University Medical
Center experience. Head Neck 2015;37:573–8
9 Braakhuis BJ, Brakenhoff RH, Leemans CR. Gene expression
profiling in head and neck squamous cell carcinoma. Curr
Opin Otolaryngol Head Neck Surg 2010;18:67–71
10 Hunt JL, Barnes L, Lewis JS Jr, Mahfouz ME, Slootweg PJ,
Thompson LD et al. Molecular diagnostic alterations in squa-
mous cell carcinoma of the head and neck and potential diagnos-
tic applications. Eur Arch Otorhinolaryngol 2014;271:211–23
11 Brandwein-Gensler M, Smith RV. Prognostic indicators in head
and neck oncology including the new 7th edition of the AJCC
staging system. Head Neck Pathol 2010;4:53–61
12 Mehanna H, Paleri V, Robson A, Wight R, Helliwell T.
Consensus statement by otorhinolaryngologists and pathologists
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on the diagnosis and management of laryngeal dysplasia. Clin 17 Stenman G, Persson F, Andersson MK. Diagnostic and thera-
Otolaryngol 2010;35:170–6 peutic implications of new molecular biomarkers in salivary
13 Gale N, Blagus R, El-Mofty SK, Helliwell T, Prasad ML, gland cancers. Oral Oncol 2014;50:683–90
Sandison A et al. Evaluation of a new grading system for 18 Cross P, Chandra A, Giles T, Johnson S, Kocjan G, Poller D et al.
laryngeal squamous intraepithelial lesions – a proposed unified Guidance on the Reporting of Thyroid Cytology Specimens.
classification. Histopathology 2014;65:456–64 London: Royal College of Pathologists, 2009
14 Smith PA, Giles TE. Fine needle aspiration cytology of head and
neck diseases: advantages and limitations. Diag Histopathol Address for correspondence:
2010;16:287–94 Timothy R. Helliwell,
15 Denton K, Smith P, Giles T, Chandra A, Desai M. Tissue Department of Cellular Pathology,
Pathways for Exfoliative Cytology and Fine Needle Aspiration Liverpool Clinical Laboratories,
Cytology. London: Royal College of Pathologists, 2010 University of Liverpool,
16 Sobin LH, Gospodarowicz MK, Wittekind C. UICC TNM Classi- Liverpool, UK
fication of Malignant Tumours. Wiley-Blackwell, Chichester,
2009 E-mail: trh@liverpool.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S66–S67. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000463

Radiotherapy in head and neck

cancer management: United Kingdom National
Multidisciplinary Guidelines

C NUTTING

Head and Neck Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. Radiotherapy is one of the key treatment modalities used in head and neck cancer
management. This paper summarises the current role and some of the recent advances in radiotherapy in head
and neck cancer management.

Radiotherapy (RT) and surgery are the two most fre-
quently used therapeutic modalities in head and neck
cancer. For early-stage tumours in many sites, surgical
excision or RT have similar cure rates but have a differ-
ent side-effect profile. Radiotherapy traditionally
offered higher rates of organ preservation and for
some cancers where function is important, it is the treat-
ment of choice. For example, RT allows preservation of
natural speech and swallowing in carcinomas of the
larynx and tongue base.1 At other sites (e.g. carcinoma
of the oral cavity), surgical excision alone may be cura-
tive and be associated with a very satisfactory function-
al outcome. The choice of treatment modality therefore
depends on individual factors including patient
preference.
For an advanced squamous cell carcinoma of the
head and neck, single modality treatment (either
surgery or RT alone) is associated with poor outcomes.
For these tumours, the combined use of surgery and
post-operative RT or use of combined chemotherapy
and radiation schedules frequently offer the highest
chance of achieving cure.
In recent years, RT has benefited from advances in
cancer imaging, treatment planning computer software
and developments in radiation delivery technology. It is
now one of the most technology-driven branches of
medicine. Typically head and neck cancer patients
will have radiation therapy which is based on the
state-of-the-art imaging technology including com-
puted tomography, magnetic resonance imaging, posi-
tron emission tomography or other imaging techniques.
Optimisation of treatment planning is performed on
high-speed computer software, which intelligently
selects the most appropriate beam directions and
shapes. Treatment is delivered by computer-driven
linear accelerators with sub-millimetre accuracy allow-
ing radiation to be focused on the tumour bearing
tissues and minimising radiation to normal tissue
structures.
Intensity-modulated radiotherapy (IMRT) is now an
established form of radiation therapy which allows
better control of radiation dose delivery in the head
and neck. In a randomised trial performed in the UK,
IMRT has been shown to reduce radiation-induced xer-
ostomia (the main long-term side effect of the standard
RT) from 75 to 39 per cent ( p = 0.004) at 12 months
following treatment.2 A similar result has been demon-
strated for patients with nasopharyngeal cancer.3
Intensity-modulated radiotherapy in now used to treat
70–80 per cent of patients with advanced head and
neck cancer, where sparing of salivary glands is
required.
Improvements in local tumour control have been
demonstrated with accelerated (delivery of radiation
over a shorter time period) or hyperfractionated (deliv-
ery of a higher dose of radiation by two to three low-
dose fractions per day) RT. These treatments have not
shown consistent improvements in overall survival,
and for that reason have not been adopted widely
outside of North America.4
Particle therapy such as with protons or stereotactic
RT may allow additional advantages to patients with
tumours close to particularly radiosensitive organs
such as the brain, spinal cord or in children’s cancers.
Presently, proton therapy is not available in the UK,
but the NHS Proton Clinical Reference Panel can
RADIOTHERAPY IN HEAD AND NECK CANCER MANAGEMENT: UK GUIDELINES
approve treatment abroad for adult head and neck
cancer patients with base of skull chordoma or chrodro-
sarcoma, as well as a variety of paediatric cancers. UK
proton facilities at The Christie Hospital in Manchester
and University College Hospital in London will be
treating patients within the next few years and addition-
al indications for head and neck cancer patients may
become apparent based on future research.
In a large meta-analysis of 93 trials and over 17 000
patients, concomitant chemotherapy (given during RT)
was shown to improve locoregional control rates and
was associated with a 6.5 per cent increase in survival
( p < 0.0001).5,6 The benefits were largely confined to
chemotherapy given during RT rather than the adjuvant
or neo-adjuvant setting. In addition, combining chemo-
therapy with radiation improves the rates of organ con-
servation. Cisplatin chemotherapy schedules are the
most effective.
Similarly the concurrent administration of cetuxi-
mab, an anti-epidermal growth factor receptor anti-
body, with RT, was shown to increase overall
survival and locoregional control in this setting.7,8
This was the first demonstration of activity of a bio-
logically targeted therapy in cancer treatment.
In the post-operative setting, two randomised con-
trolled trials have demonstrated the use of concomitant
cisplatin during radiation to increase tumour control
and overall survival in high-risk patients with positive
resection margins or extracapsular lymph node
spread.9,10
While concomitant chemotherapy has a proven role
in improving outcomes for head and neck cancer, the
role of neo-adjuvant chemotherapy remains controver-
sial. Two large studies suggested that the use of doce-
taxel, cisplatin and 5-fluorouracil prior to definitive RT
improved survival.11,12 The use of non-standard RT
and/or chemoradiation schedules in these trials has
led to uncertainty as to the benefits of this approach
when a standard chemoradiation is prescribed.
Induction chemotherapy is now becoming less fre-
quently used, and its benefit is probably limited to
patients who are at high risk of systemic metastatic
spread.
There is increasing evidence that human papilloma
virus-related oropharyngeal cancer has an excellent
outcome with chemoradiotherapy and that less inten-
sive RT schedules may be more appropriate, which is
currently being investigated.
Key points
• Radiotherapy is a key modality in the treatment of
head and neck cancer
• Conformal radiotherapy planning and chemora-
diation techniques should be available in all treat-
ment centres
S67
• Intensity-modulated radiotherapy has been shown
to reduce long-term xerostomia and should be
offered to all appropriate patients.
References
1. Denaro N, Russi EG, Lefebvre JL, Merlano MC. A systematic
review of current and emerging approaches in the field of larynx
preservation. Radiother Oncol 2014;110:16–24
2. Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA,
Clark C et al. Parotid-sparing intensity modulated versus conven-
tional radiotherapy in head and neck cancer (PARSPORT): a
phase 3 multicentre randomised controlled trial. Lancet Oncol
2011;12:127–36
3. Kam MK, Leung SF, Zee B, Chau RM, Suen JJ, Mo F et al.
Prospective randomized study of intensity-modulated radiother-
apy on salivary gland function in early-stage nasopharyngeal
carcinoma patients. J Clin Oncol 2007;25:4873–9
4. Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL
et al. A Radiation Therapy Oncology Group (RTOG) phase III
randomized study to compare hyperfractionation and two var-
iants of accelerated fractionation to standard fractionation radio-
therapy for head and neck squamous cell carcinomas: first
report of RTOG 9003. Int J Radiat Oncol Biol Phys 2000;48:
7–16
5. Pignon JP, le Maitre A, Maillard E, Bourhis J, Group M-NC.
Meta-analysis of chemotherapy in head and neck cancer
(MACH-NC): an update on 93 randomised trials and 17,346
patients. Radiother Oncol 2009;92:4–14
6. Blanchard P, Baujat B, Holostenco V, Bourredjem A, Baey C,
Bourhis J et al. Meta-analysis of chemotherapy in head and
neck cancer (MACH-NC): a comprehensive analysis by
tumour site. Radiother Oncol 2011;100:33–40
7. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB
et al. Radiotherapy plus cetuximab for squamous-cell carcinoma
of the head and neck. N Engl J Med 2006;354:567–78
8. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK
et al. Radiotherapy plus cetuximab for locoregionally advanced
head and neck cancer: 5-year survival data from a phase 3 ran-
domised trial, and relation between cetuximab-induced rash and
survival. Lancet Oncol 2010;11:21–8
9. Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL,
Greiner RH et al. Postoperative irradiation with or without con-
comitant chemotherapy for locally advanced head and neck
cancer. N Engl J Med 2004;350:1945–52
10. Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J,
Saxman SB et al. Long-term follow-up of the RTOG 9501/
intergroup phase III trial: postoperative concurrent radiation
therapy and chemotherapy in high-risk squamous cell carcin-
oma of the head and neck. Int J Radiat Oncol Biol Phys
2012;84:1198–205
11. Posner MR, Hershock DM, Blajman CR, Mickiewicz E,
Winquist E, Gorbounova V et al. Cisplatin and fluorouracil
alone or with docetaxel in head and neck cancer. N Engl J
Med 2007;357:1705–15
12. Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R,
Degardin M et al. Cisplatin, fluorouracil, and docetaxel in unre-
sectable head and neck cancer. N Engl J Med 2007;357:
1695–1704
Address for correspondence:
Chris Nutting,
Head and Neck Unit,
The Royal Marsden NHS Foundation Trust and
Institute of Cancer Research,
London, UK
E-mail: chris.nutting@rmh.nhs.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S68–S70. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000475

Surgery in head and neck cancer: United Kingdom

National Multidisciplinary Guidelines

J J HOMER1,2
1
Manchester Royal Infirmary, Manchester, UK, and 2Otolaryngology – Head and Neck Surgery, Manchester
Academic Health Sciences Centre, University of Manchester, Manchester, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. Surgery is one of the key modalities used in head and neck cancer treatment. Recent
advances and a greater awareness of the short- and long-term toxicities associated with non-surgical modalities
and newer technologies that permit minimal access resections have led to a resurgence in surgery. This paper
provides an overview of the role of surgery in head and neck cancer practice.

The aim of surgery with curative intent in head and
neck cancer (HNC) is complete microscopic surgical
excision. Excision margins are a consistent prognostic
factor1–3 and a major consideration for more radical
post-operative adjuvant therapy (and therefore more
attendant morbidity),4 with the possible exception of
thyroid cancer.5 Whilst there has been considerable
progress with less invasive surgical access techniques,
the underlying principle of profound importance in
head and neck surgery is that surgical resection
achieves complete, microscopic clearance of the
tumour with the appropriate safely margin according
to the type, site and stage of cancer. There is virtually
no oncological role for debulking surgery in order to
improve the chances of cure with subsequent chemora-
diation. Debulking may be necessary for airway preser-
vation and for symptom palliation, however.
One of the most prominent surgical advances of
recent times has been the development and popularisa-
tion of transoral access techniques for oropharyngeal,
supraglottic and glottic cancers, via transoral laser
microsurgery (TLM) and transoral robotic surgery
(TORS). Transoral robotic surgery should be seen as
an evolutionary refinement of TLM, especially useful
for tongue base and supraglottic resections, and the evi-
dence for these procedures should be considered
together. When minimal access surgery is compared
to open techniques, the advantages relating to reduction
in morbidity are obvious. This applies to endoscopic
approaches for sinonasal tumour resection, either with
or without craniotomy. Here, the relevant comparison
is to open transfacial access techniques, and the advan-
tages of less radical access are obvious, with no
compromise in prognosis (at least in selected cases).6
Any surgeon managing sinonasal tumours should be
able to offer the full range of surgical techniques,
open and endoscopic, and, as an oncology surgeon, be
a core member of the multidisciplinary team.
However, with the transoral techniques of TLM and
TORS, the relevant comparison is really to primary
radiotherapy (RT) or chemoradiotherapy in the main.
Even in glottic cancer, it has only been shown that
there is equipoise between TLM and RT for T1a.7.
There is less robust evidence for T1b cancers8 and
clearly insufficient data for T2 glottic cancers and for
supraglottic cancers. For oropharyngeal cancers, there
is much work to do in order to define the role of trans-
oral surgery in place of, or in concert with, chemoradia-
tion.9 Much of this depends on whether and how post-
operative RT and chemoradiotherapy can be modified
in patients treated with primary surgery, and, especially
for oropharyngeal cancer, the influence of human pap-
illoma virus status and neck metastases. There appears
to be consistent evidence that swallowing outcomes
may be better in patients treated primarily with
surgery, if post-operative treatment can be restricted
to RT only and perhaps to a lower dose.10–12
A further issue with transoral techniques in particular
is the proof of surgical margins. The practice of basing
this on further biopsies or submission of additional
tissue from the tumour bed has been shown to be less
reliable in glossectomy and less prognostic than defin-
ing surgical margins from the main tumour.13
However, with small tumours, especially from the
glottis, then: (a) smaller margins may be oncologically
safe; and (b) the impact of thermal artefact is such that
SURGERY IN HEAD AND NECK CANCER: UK GUIDELINES
it is difficult to prove histological clearance without
submitting separate material from the margins.3 The
same issues apply to complex resections in which it
can be very difficult for the pathologist to determine
where the true margins are, for example with anterior
and lateral skull base resections. The key is to good
interdisciplinary working between surgeon and path-
ologist. The bottom line is that the determination of
accurate surgical margins is critical, whatever the surgi-
cal technique employed.
For advanced disease, in which more radical, open
surgery is required, the issues to consider are:
• Can a complete resection be achieved? If this is
not realistic, then the morbidity of such surgery
can rarely be justified
• Even if complete resection can be achieved, is the
mortality risk and morbidity justified by the
chances of overall survival?
• If radical surgery is to be done, it should be done
comprehensively. There should be no compromise
in the extent of the resection, when the attendant
morbidity is not materially affected by a more
radical approach with appropriate reconstruction
in expert hands. This may mean pharyngolaryn-
gectomy instead of laryngectomy, mandibu-
lectomy instead of soft tissue resection only in
the oral cavity or extending a maxillectomy poster-
iorly or superiorly.
For defects that will require reconstruction with
microvascular free flaps, in most cases having two con-
sultant surgeons has obvious advantages, regardless of
specialties involved. The use of free flaps is increas-
ing.14 There has been continued evolution of recon-
struction options, with a greater variety of composite
flaps suited to the defect involved. With regard to
soft tissue reconstruction, the anterolateral thigh flap
is ideal for most soft tissue defects,15 except when a
thin flap might be required for smaller oral cavity
defects.
When applying these principles to salvage surgery,
these principles are even more important. The focus
is defining what the role of salvage surgery is (cure,
palliation) and what the chance of achieving the aim
actually is in the setting of greatly increased chances
of serious post-operative morbidity, with, in many
cases, low chance of cure.16–19
With regard to neck dissection, for many N+ cases,
conservation techniques allow the preservation of key
non-lymphatic structures and the restriction of levels
dissected according to the primary tumour and the
amount of disease. Shoulder and neck dysfunction
has been correctly recognised as an important con-
tributor to quality of life after treatment. For N0
cases, it is reasonably clear which cases require
elective neck dissection, when surgery is the primary
treatment modality. In practice, when this is the case,
the nature of surgery is such that the addition of a
S69
selective neck dissection adds little to the overall
surgery. When this is not the case, there is a role for
sentinel node biopsy.20 For neck disease treated with
RT or chemoradiotherapy, neck dissection is only
required for residual disease shown on conventional
or positron emission tomography–computed tomog-
raphy imaging.21
Training and manpower in head and neck
surgery
The situation in the UK contrasts with many other
countries, in that HNC surgery is divided between the
two major specialties of otorhinolaryngology–head
and neck surgery (ORL–HNS) and oral and maxillo-
facial surgery (OMFS), in a more equitable fashion
than most other countries. Should there continue to
be the distinction of, in general, OMFS managing
and operating on oral cavity cancer and performing
most microvascular reconstruction, with ORL–HNS
managing the pharynx, larynx and thyroid? There are
areas of overlap, but the division largely remains, irre-
spective of the influence of interface interdisciplinary
fellowships.
There is no consensus about the volume of major
surgery required in order to achieve and maintain com-
petence. Whilst there is a clear relationship between
both hospital and individual surgeon volume with
better outcomes, it is difficult to define a minimal
cut-off in terms of volumes required.22 Even with
something as easily defined as microvascular free
flap surgery (with easily measurable outcomes), it
many come as a surprise that there is no guidance on
how may free flaps a surgeon or hospital should do
per year in order to maintain and evidence competence.
In summary, the evolution of surgery for HNC con-
tinues to give rise to the ability to perform more
complex tumour ablation together with more refined
reconstruction and, at the same time, there has been sig-
nificant progress in minimal access techniques without
oncological compromise. The increasing use of che-
moradiotherapy means there is an increase in salvage
surgery (when appropriate) which always represents
the most difficult challenge for a head and neck
surgeon. These changes make the need for the clarifica-
tion of training and minimal volumes for surgeons and
hospitals even more important.
References
1. Smits RW, Koljenovic S, Hardillo JA, Ten Hove I, Meeuwis
CA, Sewnaik A et al. Resection margins in oral
cancer surgery: room for improvement. Head Neck 2016;
38(Suppl 1):E2197–203
2. Luryi AL, Chen MM, Mehra S, Roman SA, Sosa JA, Judson
BL. Treatment factors associated with survival in early-stage
oral cavity cancer: analysis of 6830 cases from the National
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2015;141:593–8
3. Hinni ML, Ferlito A, Brandwein-Gensler MS, Takes RP, Silver
CE, Westra WH et al. Surgical margins in head and neck
cancer: a contemporary review. Head Neck 2013;35:1362–70
4. Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH,
Saxman SB et al. Postoperative concurrent radiotherapy and
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chemotherapy for high-risk squamous-cell carcinoma of the
head and neck. N Engl J Med 2004;350:1937–44
5. Wang LY, Ghossein R, Palmer FL, Nixon IJ, Tuttle RM, Shaha
AR et al. Microscopic positive margins in differentiated thyroid
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2015;25:993–8
6. Meccariello G, Deganello A, Choussy O, Gallo O, Vitali D,
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7. O’Hara J, Markey A, Homer JJ. Transoral laser surgery versus
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carcinoma: systematic review of local control outcomes.
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8. Hoffmann C, Cornu N, Hans S, Sadoughi B, Badoual C, Brasnu
D. Early glottic cancer involving the anterior commissure
treated by transoral laser cordectomy. Laryngoscope 2015.
doi: 10.1002/lary.25757
9. Yeh DH, Tam S, Fung K, MacNeil SD, Yoo J, Winquist E et al.
Transoral robotic surgery vs. radiotherapy for management of
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10. Chen AM, Daly ME, Luu Q, Donald PJ, Farwell DG.
Comparison of functional outcomes and quality of life
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11. O’Hara J, Cosway B, Muirhead C, Leonard N, Goff D,
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C et al. Functional swallowing outcomes following transoral
robotic surgery vs primary chemoradiotherapy in patients
with advanced-stage oropharynx and supraglottis cancers.
JAMA Otolaryngol, Head Neck Surg 2013;139:43–8
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BG, Canis M, Purgina B et al. Early oral tongue squamous
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2015;141:1104–10
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Clarke PM et al. Role of reconstructive surgery in the manage-
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11,841 reconstructions. J Plast Reconstr Aesthet Surg 2015;68:
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15. Park CW, Miles BA. The expanding role of the anterolateral
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17. Matoscevic K, Graf N, Pezier TF, Huber GF. Success of salvage
treatment: a critical appraisal of salvage rates for different sub-
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S et al. Selection of ideal candidates for surgical salvage of head
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2015;141:1059–65
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Head Neck 2014;36:1820–34
Address for correspondence:
Prof Jarrod Homer,
Manchester Royal Infirmary,
Otolaryngology – Head and Neck Surgery,
Manchester Academic Health Sciences Centre,
University of Manchester, Manchester, UK
E-mail: jarrod.j.homer@manchester.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S71–S74.
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000840
Chemotherapy: United Kingdom National
Multidisciplinary Guidelines
C G KELLY
Northern Centre for Cancer Care and Newcastle University, Freeman Hospital, Newcastle upon Tyne, UK
Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. This paper summarises the role of chemotherapy in head and neck cancer management,
recent advances and what the future holds for this modality.
Introduction
Chemotherapy alone cannot cure head and neck cancer.
It is used in conjunction with other treatments, surgery
and radiotherapy (RT), to improve outcomes in terms
of local control, organ preservation with continued
organ function and to decrease the incidence of sub-
clinical micro-metastatic spread.
Chemotherapy is not given routinely for early
primary T1/T2 disease without nodal involvement.
Chemotherapy is given for its direct tumouricidal
effect, at both the local primary and distant metastatic
sites. If given with RT it can have a radio sensitising
effect, making cancer cells more susceptible to RT
and increasing the cancer cell kill. It may be used as
induction chemotherapy (ICT), almost always before
RT rather than surgery. If ICT is used, further chemo-
therapy is usually given with subsequent RT, and this
is known as sequential chemotherapy. More common-
ly, chemotherapy is given only concurrently with radio-
therapy (combined chemoradiotherapy) with only a
minority of patients having induction or sequential
regimens. Combined chemoradiotherapy has been
shown to improve local control and increase survival
where primary surgery has been the definitive treat-
ment in selected populations.
Induction (neoadjuvant) chemotherapy
The response to neoadjuvant chemotherapy could give
important prognostic information, as it can act as a sur-
rogate marker for response to later treatment.
This latter advantage was used in one of the earliest
trials of neoadjuvant chemotherapy for organ preserva-
tion, the ‘Veterans’ trial,1 where patients were given
two cycles of cisplatin and 5-fluorouracil (5-FU), and
if there was a response to chemotherapy patients went
on to have chemotherapy and RT, but if there was no
response, the patients went directly to laryngectomy.
Induction chemotherapy is considered beneficial for
several reasons. If ICT could shrink primary tumour
GUIDELINE
volumes before the principal treatment of RT or che-
moradiotherapy, this might allow better blood flow
into the tumour allowing a greater tumouricidal dose
of drugs into the tumour and decrease the volume of
hypoxic areas which would decrease the radio-resist-
ance that hypoxic cancer cells show. Improved local
control would lead to a greater chance of organ preser-
vation and functionality. Since surgery and RT are both
locoregional treatments, ICT could theoretically treat
distant subclinical metastatic disease. The response to
ICT could give important prognostic information, as
it can act as a surrogate marker for response to later
treatment.
One of the main evidence sources for the use of
chemotherapy in head and neck cancer is the Meta-ana-
lysis of Chemotherapy in Head and Neck Cancer
(MACH-NC) which was originally published in 2000
and updated in 2007 and 2009.2 This overview
reviewed 87 trials containing data on over 16 000
patients, with overall survival as the primary endpoint.
There was no overall survival benefit with the use of
ICT when compared with primary surgery or RT
alone, although cisplatin and 5-FU delivered as com-
bined chemoradiotherapy did show some benefit. It
also suggested that ICT may reduce the incidence of
distant metastases more effectively than combined
chemoradiotherapy.
Debate continues as to whether ICT followed by
combined chemoradiotherapy is more beneficial than
combined chemoradiotherapy alone. Some large
trials, such as the Spanish Head and Cancer Corpora-
tive Group trial have shown no benefit,3 while others,
such as a large Italian trial comparing ICT followed
by combined chemoradiotherapy to combined chemo-
radiotherapy alone showed significantly improved
overall survival for the former arm.4 Interest was
rekindled in ICT when two trials, one European, and
one from North America, TAX 3235 and TAX 3246
showed a benefit by including a taxane, such as
S72
docetaxel or paclitaxel in the chemotherapy regimen in
addition to cisplatin and 5-FU. The evidence suggested
that adding a taxane, such as docetaxel or paclitaxel to
cisplatin and 5-FU, i.e. docetaxel/cisplatin/5-FU
(TPF) vs cisplatin/5-FU (PF) did improve survival in
the TPF arm, but at a cost of much higher toxicity.
However, these trials have been criticised for not
using optimal concurrent chemotherapy schedules.
Based on further phase 3 studies (DeCIDE,7
PARADIGM trial and8 TREMPLIN study9) the evi-
dence to date does not suggest ICT is in general bene-
ficial in head and neck cancer.
Usually, induction and sequential regimens are
offered to patients with good performance status,
fewer comorbidities and those with bulky nodal
disease, stage N2b and above, and where surgery is
not appropriate.
Concurrent or concomitant chemotherapy
The main advantage of combined chemoradiotherapy,
over sequential chemotherapy, is the reduced chance
of patients having to stop treatment because of toxicity,
and resulting in breaks in RT, which is radiobiologically
suboptimal and can be detrimental to treatment outcome.
In the MACH-NC trial,2 the use of combined che-
moradiotherapy showed that it gave a survival benefit
when added to RT alone, giving a 6.5 per cent decrease
in mortality at five years, in absolute terms. This benefit
was not seen in patients over 70 years of age. The most
commonly used combined chemoradiotherapy regi-
mens are cisplatin 100 mg/m2 on days 1, 22 and 43
of RT, either alone or with 5-FU, 1 g/day on days
1–4, and then repeated 3 weekly with cisplatin. If 5-
FU is added, the cisplatin dose is usually reduced.
Although this regimen is commonly used, there are
few direct comparisons with other combined chemora-
diotherapy within randomised controlled trials.
Increased toxicity produced by adding platinum
chemotherapy to RT can be considerable. A significant
proportion of patients do not receive all three cycles of
chemotherapy because of toxicity, but one study has
shown no survival difference in patients receiving
two cycles of cisplatin rather than three cycles, but
the RT given was not identical within the arms of
this study.10 chemotherapy toxicity can also interfere
detrimentally with RT delivery causing breaks during
treatment which are associated with poorer outcomes.
If cisplatin is contraindicated because of renal func-
tion status, the presence of neuropathy, tinnitus or deaf-
ness, or where there is a danger of fluid overload with
the necessary pre-hydration used in cisplatin adminis-
tration, carboplatin can be considered as it causes less
nephrotoxicity, ototoxicity and peripheral neuropathy
but is more myelosuppressive. It is not thought to be
as tumouricidal as cisplatin and for this reason it has
now been largely overtaken by the epidermal growth
factor receptor inhibitor, cetuximab in clinical practice
when cisplatin is contraindicated.
HC G KELLY
Concurrent radio-sensitisers
It is known that tumour cell hypoxia induces radioresis-
tance, and there has been renewed interest in giving
hypoxic cell radiosensitising drugs during RT. The
two most common in use are the antihelminthic drug
nimorazol, which is extensively used in some parts of
Europe, and tirapazamine, an anticoagulant which is
activated in hypoxic environments. Although estab-
lished in some parts of the world, trials are ongoing
with these agents to establish efficacy and with nimor-
azol, patient tolerability.
Chemotherapy and human papilloma virus
(HPV)-positive tumours
Human papilloma virus is known to have an aetio-
logical role in inducing some head and neck cancers,
especially in the oropharynx where HPV infection
may be linked to 50–80 per cent of tumours. There is
evidence from several studies that outcomes are better
following treatment in patients with HPV-positive
tumours. There is also growing evidence that continu-
ing to smoke negates the outcome benefit associated
with HPV positivity.
Given the good prognosis, the question arises if
HPV-positive cancers are being overtreated with stand-
ard head and neck chemoradiotherapy regimens and
being given unnecessary morbidity. At present there is
not enough evidence to alter chemotherapy or indeed
RT treatment regimens depending on the patient’s
HPV status, outside of the context of a clinical trial.
Several trials are now investigating these questions,
most using cetuximab comparing with cisplatin (see
below). These include the RTOG 1016 in the USA,
the De-ESCALATE HPV study in the UK and the
Trans-Tasman Radiotherapy Group 12.01 study in
Australia.
Targeted biological agents
Targeted therapy in head and neck cancer developed
with the recognition that epidermal growth factor
receptor (EGFR) is overexpressed in the majority of
head and neck cancers, up to 90 per cent in some
studies, and is associated with a poorer prognosis.
When a growth factor attaches to its receptor on the
cell surface, cells are stimulated to divide and conse-
quently tumours grow. If the receptor is abnormal
because of a mutation the stimulation to divide may
even occur without growth factors interacting with
the receptor. Cetuximab is a mouse–human chimaeric
monoclonal antibody which binds to the extracellular
portion of EGFR and turns this signalling system off.
In the initial innovative cetuximab trial by Bonner
et al.,11 patients with advanced head and neck cancer
were randomised to receive radical RT with or
without cetuximab. At three years, survival (55 vs 45
per cent) and local control (50 vs 41 per cent) was
better in the patient group who had received cetuxi-
mab.12 Although these initial results were encouraging,
CHEMOTHERAPY IN HEAD AND NECK CANCER: UK GUIDELINES
a major drawback to the study was that, since the study
had started, RT alone as used in this study had been
overtaken as a standard of care by combined chemora-
diotherapy. So, comparing radiation alone vs radiation
plus cetuximab was much less relevant in the context
of contemporary standard practice. Also in the initial
trial patients were not stratified by HPV status.
Despite initial hopes that cetuximab would give less
toxicity than the standard chemotherapy, and can there-
fore be given to older patients and those with a poorer
performance status, it has been shown to have a differ-
ent, although not necessarily less toxic, morbidity profile
in the form of grade 3 and 4 radiation dermatitis. Patients
may also develop an acne-like rash predominantly over
the face, neck and trunk with a more eczema-like condi-
tion at the fingertips and elbows. In a minority of
patients this reaction can be so severe that cetuximab
may need to be stopped as these side effects can
usually be managed by increasing the treatment interval
and supportive care with topical medications. There is
some suggestion that patients who develop this rash
may also have a better tumour response with improved
overall survival.
Other targeted EGFR monoclonal antibodies are
under investigation such as panitumamab or zalutumu-
mab, but to date with less encouraging results showing
no improvement in overall survival.
Another potential target further down this biological
pathway, offering a different mechanism of action is
used by erlotinib, a small molecule inhibitor of
EGFR tyrosine kinase. One phase II trial of erlotinib
given alone or combined with cisplatin, unfortunately
did not show any benefit in outcome for the combin-
ation. Despite this other targets in the epidermal
growth factor receptor pathway are being investigated.
Chemotherapy for recurrent or metastatic
head and neck cancer
Chemotherapy or targeted biological agents may be
indicated for patients with recurrent and/or metastatic
disease but prognosis for patients with metastatic
disease has a median survival of approximately 6–12
months in most studies.
Appropriateness of chemotherapy depends on
several factors such as extent and burden of disease;
whether symptoms are present or not; whether failure
of control has taken place at the primary site only;
and whether there is metastatic disease only or both.
The most important factor often is the fitness and per-
formance status of the patient and whether they could
tolerate the proposed chemotherapy, and how much it
would reduce their pre-treatment quality of life, for
whatever limited survival period they have.
Locoregional failure
In this group of patients where salvage surgery or
retreatment with RT or combined chemoradiotherapy
is being considered, it is important to be aware if
distant metastatic disease is also present and also to
S73
establish that the locoregional recurrent disease is not
a second primary head and neck cancer. Discovering
that metastatic disease is also present is not an absolute
contraindication to salvage treatments at the primary
site, as locoregional failure and metastatic disease can
be considered as two separate problems in the patient’s
management plan. If good palliation at the primary site
or locoregionally can be achieved relatively easily, by a
salvage procedure, the presence of metastatic disease,
especially small volume metastatic disease, should
not necessarily stop treatment to the primary or locore-
gional site. The patients who do better with salvage
treatment are those with smaller volumes of recurrence,
a longer disease-free interval and less comorbidity.
Some particular head and neck subsites such as the
larynx, also have better outcomes.13
Distant metastases
Chemotherapy is often indicated here, as part of a best
supportive care package to improve symptoms, but has
not been shown to significantly extend survival. The
therapeutic window for giving chemotherapy in this
situation would be when the patient still has an appro-
priate performance status to receive and benefit from
chemotherapy, with the trade-off being, an improved
symptom state for the inevitable morbidity caused by
the chemotherapy. The choice of regimen depends on
factors such as performance status, comorbidities,
renal function, estimated physiological reserve of the
patient and the interval since last chemotherapy.
If chemotherapy is to be given for distant metastatic
disease then which regimen is most appropriate
depends on several factors including performance
status, comorbidities present, renal function and the
estimated physiological reserve of the patient. Also
which regimens the patients had before and the interval
since last chemotherapy may be important.
The most common regimens used are cisplatin or
carboplatin with 5-FU. These give an expected
response rate of approximately 30 per cent.
Carboplatin is used more in this palliative metastatic
setting than with induction or concurrent regimens,
because although deemed slightly less effective than
cisplatin; its less toxic side-effect profile, can be seen
to be more appropriate in the palliative setting.
Elderly patients do appear to respond to platinum-
based chemotherapy in the metastatic setting,14 in con-
trast to a lack of benefit in the elderly when used in
primary chemoradiotherapy regimens. Other more
toxic chemotherapy regimens have also been investi-
gated using platinum and a taxane (docetaxel or pacli-
taxel), in combination, but no survival benefit has been
demonstrated.
Cetuximab added to cisplatin and 5-FU, can increase
both response rate and improve short-term survival
slightly as shown in the EXTREME trial,15 but five-
year follow-up published recently in abstract form
shows very low survival for patients in both arms of
the study. The EXTREME study did not allow
S74
crossover between regimens, so similar results might be
achieved by the use of cisplatin and 5-FU followed by
cetuximab used sequentially. In patients who have
become refractive to cisplatin and 5-FU, cetuximab as
a single agent does have a low response rate of approxi-
mately 10–15 per cent.16,17
Key points
• Concurrent chemoradiotherapy is at present the
standard of care for treatment of locally advanced
head and neck cancer with a confirmed survival
benefit of 6.5 per cent at five years
• Single agent cisplatin, which in the past has been
shown to be as effective as multiple drug regimes,
is now being challenged by the introduction of the
use of taxanes
• Targeted biological agents, such as cetuximab,
have a role to play in both advanced head and
neck cancer and recurrent or metastatic disease
but those roles are still being established
• At present human papilloma virus status does not
alter management regimens, although there are
multiple studies underway examining if less
intense treatment, both with radiotherapy and
chemotherapy, could be given to achieve the
same outcome but with less toxicity
• The potential benefit of neoadjuvant or induction
chemotherapy is being re-examined now, but most
recent work has not shown a substantial benefit
• Elderly patients benefit least in terms of survival
advantage with the use of concurrent chemotherapy.
References
1 The Department of Veterans Affairs Laryngeal Cancer Study
Group. Induction chemotherapy plus radiation compared with
surgery plus radiation in patients with advanced laryngeal
cancer. N Engl J Med 1991;324:1685–90
2 Pignon JP, le Maitre A, Maillard E, Bourhis J, Group M-NC.
Meta-analysis of chemotherapy in head and neck cancer
(MACH-NC): an update on 93 randomised trials and 17,346
patients. Radiother Oncol 2009;92:4–14
3 Hitt R, Grau JJ, Lopez-Pousa A, Berrocal A, García-Girón C,
Irigoyen A et al. A randomized phase III trial comparing induc-
tion chemotherapy followed by chemoradiotherapy versus che-
moradiotherapy alone as treatment of unresectable head and
neck cancer. Ann Oncol 2014;25:216–25
4 Ghi MG, Paccagnella A, Ferrari D. Concomitant chemoradiation
(CRT) or cetuximab/RT (CET/RT) versus induction
Docetaxel/ Cisplatin/5-Fluorouracil (TPF) followed by CRT
or CET/RT in patients with Locally Advanced Squamous
Cell Carcinoma of Head and Neck (LASCCHN). A randomized
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Winquist E, Gorbounova V et al. Cisplatin and fluorouracil
HC G KELLY
alone or with docetaxel in head and neck cancer. N Engl J
Med 2007;357:1705–15
6 Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R,
Degardin M et al. Cisplatin, fluorouracil, and docetaxel in unre-
sectable head and neck cancer. N Engl J Med 2007;357:
1695–704
7 Cohen EE, Karrison TG, Kocherginsky M, Mueller J, Egan R,
Huang CH et al. Phase III randomized trial of induction chemo-
therapy in patients with N2 or N3 locally advanced head and
neck cancer. J Clin Oncol 2014;32:2735–43
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D et al. Induction chemotherapy followed by concurrent che-
moradiotherapy (sequential chemoradiotherapy) versus concur-
rent chemoradiotherapy alone in locally advanced head and
neck cancer (PARADIGM): a randomised phase 3 trial.
Lancet Oncol 2013;14:257–64
9 Lefebvre JL, Pointreau Y, Rolland F, Alfonsi M, Baudoux A,
Sire C et al. Induction chemotherapy followed by either chemor-
adiotherapy or bioradiotherapy for larynx preservation: the
TREMPLIN randomized phase II study. J Clin Oncol 2013;
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10 Ang K, Zhang Q, Wheeler RH. A phase III trial (RTOG 0129) of
two radiation-cisplatin regimens for head and neck carcinomas
(HNC): impact of radiation and cisplatin intensity on outcome.
J Clin Oncol 2010;28(Suppl 15):5507
11 Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB
et al. Radiotherapy plus cetuximab for squamous-cell carcinoma
of the head and neck. N Engl J Med 2006;354:567–78
12 Bonner JA, Harari PM, Giralt J et al. Radiotherapy plus cetux-
imab for locoregionally advanced head and neck cancer: 5-year
survival data from a phase 3 randomised trial, and relation
between cetuximab-induced rash and survival. Lancet Oncol
2010;11:21–8
13 Spencer SA, Harris J, Wheeler RH, Machtay M, Schultz C,
Spanos W et al. Final report of RTOG 9610, a multi-institutional
trial of reirradiation and chemotherapy for unresectable recurrent
squamous cell carcinoma of the head and neck. Head Neck
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Outcome of elderly patients with recurrent or metastatic head
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Rottey S et al. Platinum-based chemotherapy plus cetuximab
in head and neck cancer. N Engl J Med 2008;359:1116–27
16 Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E,
Rolland F et al. Open-label, uncontrolled, multicenter phase II
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Address for correspondence:
Charles G Kelly,
Northern Centre for Cancer Care and Newcastle University,
Freeman Hospital,
Newcastle upon Tyne, UK
E-mail: Charles.Kelly@nuth.nhs.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S75–S82. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000487

Laryngeal cancer: United Kingdom National

Multidisciplinary guidelines

T M JONES1, M DE2, B FORAN3, K HARRINGTON4, S MORTIMORE2

1
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Aintree University Hospitals
NHS Foundation Trust, Liverpool, 2Department of ENT–Head and Neck Surgery, Derby Royal Hospitals NHS
Foundation Trust, Derby, 3Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, and 4The Institute of
Cancer Research, Royal Marsden Hospital NHS Trust, London, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. Significantly new data have been published on laryngeal cancer management since the last
edition of the guidelines. This paper discusses the evidence base pertaining to the management of laryngeal
cancer and provides updated recommendations on management for this group of patients receiving cancer care.

Recommendations
• Radiotherapy (RT) and transoral laser microsurgery (TLM) are accepted treatment options for T1a–T2a glottic
carcinoma. (R)
• Open partial surgery may have a role in the management of selected tumours. (R)
• Radiotherapy, TLM and transoral robotic surgery are reasonable treatment options for T1–T2 supraglottic
carcinoma. (R)
• Supraglottic laryngectomy may have a role in the management of selected tumours. (R)
• Most patients with T2b–T3 glottic cancers are suitable for non-surgical larynx preservation therapies. (R)
• Concurrent chemoradiotherapy should be regarded as the standard of care for non-surgical management. (R)
• Subject to the availability of appropriate surgical expertise and multi-disciplinary rehabilitation services, TLM
or open partial surgical procedures ± post-operative RT, may be also be appropriate in selected cases. (R)
• In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-
operative RT) is recommended to at least lymph node levels II, III and IV bilaterally. In node positive disease, it
is recommended that lymph node levels II–V should be treated on the involved side. If level II nodes are
involved, then elective irradiation of ipsilateral level Ib nodes may be considered. (R)
• Most patients with T3 supraglottic cancers are suitable for non-surgical larynx preservation therapies. (R)
• Concurrent chemoradiotherapy should be regarded as the standard of care for non-surgical management. (R)
• Subject to the availability of appropriate surgical expertise and multi-disciplinary rehabilitation services, TLM
or open partial surgical procedures ± post-operative RT, may also be appropriate in selected cases. (R)
• In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-
operative RT) is recommended to at least lymph node levels II, III and IV bilaterally. In node positive disease,
lymph node levels II–V should be treated on the involved side. (R)
• As per the PET-Neck clinical trial, patients with N2 or N3 neck disease who undergo treatment with
chemoradiotherapy to their laryngeal primary and experience a complete response with a subsequent
negative post-treatment positron emission tomography combined with computed tomography (PET–CT)
scan do not require an elective neck dissection. In contrast, patients who have a partial response to
treatment or have increased uptake on a post-treatment PET–CT scan should have a neck dissection. (R)
• Larynx preservation with concurrent chemoradiotherapy should be considered for T4 tumours, unless there is
tumour invasion through cartilage into the soft tissues of the neck, in which case total laryngectomy yields
better outcomes. (R)
• In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-
operative RT) is recommended to bilateral lymph node levels II, III, IV, V and VI. (R)
S76
Introduction
The aim of any clinician involved in the treatment of
laryngeal squamous cell carcinoma should be to cure
the disease whilst maintaining maximal laryngeal func-
tion. Whilst this seems a simple concept, deciding how
best to achieve this aim in any given patient is often dif-
ficult and results in well-rehearsed complex discussions
within multi-disciplinary team (MDT) meetings
throughout the UK on a regular basis. Underpinning
this lack of clinical certainty is a lack of level I evi-
dence, particularly with respect to the comparative
merits of surgical and non-surgical treatment modal-
ities. Thus, for most laryngeal tumours, perceived treat-
ment equipoise exists. In light of this dearth of good
quality comparative data, what treatment any given
patient receives is typically related to local MDT
dynamics and clinical resources.
Although we are unable to rectify this lack of evi-
dence, in this document we highlight the treatment
options available for any given tumour and attempt,
based on published evidence, to highlight the relative
merits or disadvantages of each approach.
During 2011, 2360 patients were diagnosed with laryn-
geal carcinoma in the UK. Of these, 1506, 108, 245 and
73 were diagnosed in England, Wales, Scotland and
Northern Ireland, respectively. Accordingly, European
Age Standardised Rates per 100 000 for England,
Wales, Scotland and Northern Ireland are 2.7, 3.0, 4.2
and 4.3, respectively; highlighting the fact that larynx
cancer is more common in Wales, Scotland and
Northern Ireland. For the UK as a whole, 1932 (82 per
cent) cases occurred in men and 428 (18 per cent) in
women (M:F; 4.5:1). Larynx cancer accounts for 1 per
cent of all cancers in men and 0.3 per cent of all
cancers in women. However, this amounts to a 22 per
cent reduction of cases diagnosed in men when compar-
ing 1992–1994 with 2009–2011. A comparable reduc-
tion (19 per cent) has occurred in women over this
timeframe. (http://info.cancerresearchuk.org/cancer-
stats/types/larynx) in keeping with the geographical
variation in incidence, larynx cancer is more commonly
diagnosed in patients of lower socio-economic groups.1
It is well documented that alcohol and tobacco, sep-
arately and synergistically are the main causes of larynx
cancer. However, in contrast to oropharynx cancer, it
appears that human papilloma virus infection is not a
major cause.2
Larynx cancer is rare in patients younger than 40
years of age, with incidence increasing with age, rising
to a peak in the eighth decade. Three-quarters of all diag-
noses occur in patients older than 60 years. (http://info.
cancerresearchuk.org/cancerstats/types/larynx)
In 2012, 618 men (79 per cent) and 166 women (21
per cent) died of larynx cancer (M:F; 3.7:1). This con-
stitutes a marked decrease – 25 and 16 per cent,
respectively – in age-standardised mortality for men
and women over the last decade. (http://info.cancerre-
searchuk.org/cancerstats/types/larynx)
T M JONES, M DE, B FORAN et al.
However, Rachet et al.1 previously demonstrated a
startling differential mortality rate between socio-eco-
nomic groups, with patients from lower socio-econom-
ic groups suffering higher death rates from larynx
cancer than those from higher socio-economic groups.
Clinical presentation
The clinical presentation of laryngeal cancer is highly
variable and depends on the site and size of the
primary tumour. Tumours of the glottis, for example,
typically present at an early stage as they manifest as
hoarseness. In comparison, tumours of the supraglottis
are likely to present later with symptoms of pain,
hoarseness or swallowing difficulty. However, it is
not uncommon for patients presenting with laryngeal
cancer to delay seeking medical advice on developing
‘early’ symptoms, only to present at a much later
stage with symptoms of pain, swallowing difficulty, a
palpable neck mass or even, in extreme cases, with
airway compromise.
Assessment and staging
As with all head and neck cancers, diagnosis of laryn-
geal cancer relies initially on good history taking and
clinical examination in the clinic. Laryngeal cancers
are, in most cases, obvious following inspection of
the larynx with a fibreoptic laryngoscope in the out-
patient department. Initial assessment of the tumour
stage relies on imaging. Whilst exact protocols vary
according to local imaging preferences, it is typical
for patients suspected of having laryngeal cancer to
undergo either magnetic resonance imaging or com-
puted tomography (CT) of the head and neck and CT
scan of the thorax and upper abdomen. The exception
to this is in patients presenting with the early stage,
T1 lesions of the glottis without anterior commissure
involvement, where imaging is unhelpful. Definitive
diagnosis is achieved by histological examination of a
tissue biopsy, obtained usually at the time of a general
anaesthetic endoscopic examination of the larynx,
pharynx and upper oesophagus. The examination
under anaesthesia is extremely important for staging
and should routinely involve inspection with rigid
(plane 0° and angled 30° and/or 70°) fibreoptic endo-
scopes. The aggregate information provided by the
imaging and the endoscopic examination facilitates the
staging of the tumour according to the tumour–node–
metastasis (TNM) system outlined below (Table I). It
is by recourse to the TNM stage of the tumour, in add-
ition to the general fitness of the patient, that treatment
decisions are ultimately made.
Management
Early (T1–T2a) glottic carcinoma
Early laryngeal cancer (T1–T2a N0 M0) is charac-
terised by low tumour volume and a low incidence of
metastatic neck disease. Consequently, the chances of
LARYNGEAL CANCER: UK GUIDELINES S77

TABLE I
TNM STAGING SYSTEM FOR LARYNGEAL CANCER
Supraglottis
T1 Tumour limited to one subsite of supraglottis with normal vocal fold mobility
T2 Tumour invades mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis
(e.g. mucosa of base of tongue, vallecula, medial wall of piriform sinus) without fixation of the larynx
T3 Tumour limited to larynx with vocal fold fixation and/or invades any of the following: post-cricoid area,
pre-epiglottic tissues, paraglottic space, and/or with minor thyroid cartilage erosion (e.g. inner cortex)
T4a Tumour invades through the thyroid cartilage and/or invades tissues beyond the larynx, e.g. trachea,
soft tissues of neck, including deep/extrinsic muscle of tongue (e.g. genioglossus, hyoglossus, palatoglossus
and styloglossus), strap muscles, thyroid and oesophagus
T4b Tumour invades pre-vertebral space, mediastinal structures or encases carotid artery
Glottis
T1 Tumour limited to vocal fold(s) (may involve anterior or posterior commissure) with normal mobility
T1a. Tumour limited to one vocal fold
T1b. Tumour involves both vocal folds
T2 T2a. Tumour extends to supraglottis and/or subglottis with normal vocal fold mobility
T2b. Tumour extends to supraglottis and/or subglottis with impaired vocal fold mobility
T3 Tumour limited to larynx with vocal fold fixation and/or invades paraglottic space, and/or with minor
thyroid cartilage erosion (e.g. inner cortex)
T4a Tumour invades through the thyroid cartilage or invades tissues beyond the larynx, e.g. trachea, soft tissues of neck,
including deep/extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus and styloglossus),
strap muscles, thyroid and oesophagus
T4b Tumour invades prevertebral space, mediastinal structures or encases carotid artery
Subglottis
T1 Tumour limited to subglottis
T2 Tumour extends to vocal fold(s) with normal or impaired mobility
T3 Tumour limited to larynx with vocal fold fixation
T4a Tumour invades through cricoid or thyroid cartilage and/or invades tissues beyond the larynx, e.g., trachea,
soft tissues of neck including deep/extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus and
styloglossus), strap muscles, thyroid and oesophagus
T4b Tumour invades prevertebral space, mediastinal structures or encases carotid artery

cure are extremely good whichever of the main treat-
ment options – radiotherapy (RT), transoral laser
microsurgery (TLM) or open partial laryngeal
surgery – is employed. A systemic review3 has con-
firmed there is insufficient evidence to determine
which of these three treatment options is most effective
for the treatment of early glottic carcinoma.
Radiotherapy with surgery in reserve or TLM are the
two most commonly used treatment modalities in the
UK. Whilst survival outcomes and local control rates
are similar,4 they have not been compared in rando-
mised trials. Individual treatment selection depends
on patient and tumour factors (e.g. indistinct tumours
diffusely infiltrating the vocal fold mucosa and larger
volume tumours involving the anterior commissure
may be more suitable for RT than transoral laser
surgery) and local expertise. Single-modality treatment
is sufficient and combining surgery with RT should be
avoided as functional outcomes (and perhaps survival
in the context of incompletely resected tumour) may
be compromised by combined-modality therapy.
Radiotherapy is delivered using megavoltage photons
from a linear accelerator (typical energies 4–6 MV);
hypofractionated RT schedules, using a fraction size
greater than 2 Gray (Gy), results in equivalent out-
comes to longer schedules, without increased toxicity.
Typical schedules include 50–52 Gy in 16 fractions
and 53–55 Gy in 20 fractions over three to four
weeks.5 Elective treatment of the neck is not recom-
mended because of the very low risk of occult nodal
disease. Radiotherapy results in significant acute
toxicity, including thick, sticky secretions, hoarse
voice, odynophagia and skin reactions. Most of these
effects resolve four to six weeks after the completion
of treatment and significant late effects are rare.
Should tumour recurrence occur, partial laryngeal
surgery provides a salvage option in appropriate clinic-
al settings, resulting in good oncological and functional
outcomes. However, these techniques are rarely offered
in the UK and, therefore, total laryngectomy is most
commonly performed.
Transoral laser microsurgery is usually undertaken
using a CO2 laser as a day case procedure and has
minimal acute morbidity. Whilst there is equipoise
with respect to voice outcome between RT and TLM
for smaller tumours, long-term quality of voice for
T2 glottic cancers is generally accepted to be better
after RT than after TLM. Voice outcome following
TLM is dependent on the extent of the resection and/
or whether the resection includes the anterior commis-
sure.4 Certain patient factors, may preclude TLM, such
as restriction of neck movement and difficult access. In
these patients, hypofractionated RT is the preferred
option.
Contrary to the practice in other countries, in the UK,
partial open surgical procedures are used less commonly
for the treatment of early de novo glottic carcinoma.
However, they provide an option for the treatment of
de novo tumours which are not accessible to TLM and
for recurrent tumours after TLM or RT. Meta-analysis
data show similar rates of local control and survival
after partial laryngectomy (comparable with TLM and
S78
RT) with larynx preservation rates of 98.3 per cent for de
novo tumours and 84.6 per cent for radio-recurrent
tumours.6,7 Open surgical procedures include laryngo-
fissure cordectomy, vertical partial laryngectomy
(VPL) ± reconstruction, frontolateral vertical partial lar-
yngectomy, supraglottic laryngectomy, supracricoid
partial laryngectomy plus cricohyoidoepiglottopexy or
cricohyoidopexy reconstruction (SCPL–CHEP or
CHP) and extended supraglottic laryngectomy.
Overall, for T1a glottic tumours the local control is
similar between RT and TLM (five-year local control
rate 90–93 per cent). In the case of T1b disease, the
local control rate is lower (85–89 per cent).
Similarly, the local control and overall survival rates
for T2a glottic cancers are comparable when treated
with TLM, partial laryngeal resection or RT.
Recommendations
• Radiotherapy and transoral laser
microsurgery are accepted treatment options
for T1a–T2a glottic carcinoma (R)
• Open partial surgery may have a role in the
management of selected tumours (R)
T1–T2 supraglottic cancers
Radiotherapy, TLM and transoral robotic surgery
(TORS) are valid treatment options for all patients
with T1–T2 supraglottic cancers. As with glottic car-
cinomas, open partial surgical procedures (supraglottic
laryngectomy) are used less commonly in the UK but
open supraglottic laryngectomy may have a role in
selected cases in units with appropriate surgical expert-
ise and multi-disciplinary support services. Survival
outcomes appear to be similar with RT and surgery
although, once again, there are no randomised com-
parative data. Whilst long-term functional (voice and
swallowing) outcomes appear similar, early swallow-
ing function is usually poorer after surgery: swallowing
rehabilitation may be prolonged and in a small propor-
tion of patients, adequate swallowing function may
never be achieved. Consequently, patient selection,
based on tumour burden and performance status, is
imperative. Again, every effort should be made to
avoid combining surgery with RT because functional
outcomes may be compromised by combined-modality
therapy.
The supraglottis has a rich lymphatic supply and, as
a consequence, the risk of nodal disease is significantly
higher for T1–T2 supraglottic cancers than for T1–T2
glottic cancers. Thus, even in the absence of clinical or
radiological evidence of nodal involvement, elective
treatment of at least bilateral lymph node levels II and
III – either with RT or selective neck dissection – is
recommended.
Whilst RT or surgery alone, is sufficient for the treat-
ment of node negative T1–T2 supraglottic cancers,
T M JONES, M DE, B FORAN et al.
concurrent platinum-based chemoradiotherapy or
surgery followed by post-operative RT is recom-
mended for node positive supraglottic carcinoma
(T1–T2 N1+, stage III–IV) in patients whose perform-
ance status is sufficient to tolerate this treatment. The
role of induction chemotherapy prior to chemora-
diotherapy or surgery remains unclear but may be
appropriate for patients presenting with advanced
nodal disease (e.g. N2c/N3), particularly if this is
rapidly progressive and/or symptomatic.
All treatment options appear to effect similar loco-
regional control and survival rates: For T1 disease,
five-year local control rates following treatment with
RT, TLM, TORS or open supraglottic laryngectomy
range from 77 to 100 per cent. For T2 tumours, the
five-year local control rates range from 80 to 97 per
cent for TLM or open supraglottic laryngectomy and
from 62 to 83 per cent for primary RT.8
Recommendations
• Radiotherapy, transoral laser microsurgery
and transoral robotic surgery are reasonable
treatment options for T1–T2 supraglottic
carcinoma (R)
• Supraglottic laryngectomy may have a role in
the management of selected tumours (R)
T2b–T3 glottic tumours
Most patients with T2b–T3 glottic cancers are suitable
for radiation-based larynx preservation therapy.
However, subject to the availability of appropriate
surgical expertise and multi-disciplinary rehabilitation
services, TLM or open partial surgical procedures ±
post-operative RT, may also be appropriate in selected
cases. Open partial surgical procedures which might be
considered include VPL ± reconstruction, frontolateral
VPL, supraglottic laryngectomy, SCPL–CHEP or CHP
and extended supraglottic laryngectomy. In the absence
of clinical or radiological evidence of nodal disease,
elective treatment (RT or surgery ± post-operative
RT) is recommended to at least lymph node levels II,
III and IV bilaterally, because of the risk of occult
nodal metastasis. Intensity-modulated radiotherapy
(IMRT) allows a convenient solution to elective
nodal treatment, enabling differential doses of RT to
be given to different nodal groups simultaneously,
depending on the presence or absence of macroscopic
disease and the risk of subclinical disease.
In node positive disease, it is recommended that
lymph node levels II-V should be treated on the
involved side. If level II nodes are involved, then elect-
ive irradiation of ipsilateral level Ib nodes may be
considered.
The potential of RT and chemotherapy for larynx
preservation was established by the landmark
Veterans Affairs Laryngeal Cancer Study Group
LARYNGEAL CANCER: UK GUIDELINES
(VALCSG) study9 in which induction chemotherapy
and RT (IC + RT) yielded similar overall survival (68
per cent at two years) to laryngectomy followed by
adjuvant RT for stage III–IV laryngeal cancer with
high rates of larynx preservation (64 per cent at two
years). Rates of salvage laryngectomy were significant-
ly lower for T3 vs T4 disease (29 per cent vs 56 per cent,
p = 0.001). Subsequently, the RTOG (Radiation
Therapy Oncology Group) 91-11 trial10 demonstrated
that concurrent chemoradiotherapy was superior to
IC + RT and RT alone in terms of laryngeal preserva-
tion (88 vs 75 vs 70 per cent, respectively, at three
years), although overall survival in each treatment arm
was similar. Of note, 10-year follow-up data have con-
firmed the superiority of concurrent chemoradiotherapy,
but a significant increase in non-cancer deaths in the
group treated with chemoradiotherapy was reported.11
The use of concurrent chemoradiotherapy for locally
advanced head and neck cancers, including laryngeal
cancers, is also supported by meta-analysis data.12
Standard concurrent chemotherapy regimens include
cisplatin (100 mg/m2) on days 1, 22 and 43 of RT
and carboplatin/5-FU on weeks 1 and 5 of RT.
Concurrent chemoradiotherapy is, however, asso-
ciated with a significant increase in acute and late tox-
icity compared with RT alone. The long-term side
effects of chemoradiotherapy are well documented:
43 per cent of patients develop severe (grade III/IV)
late toxicity, including a reduction in speech and swal-
lowing function which can lead to life-long depend-
ence on a feeding tube (13 per cent of patients two
years after treatment) and have a profound effect on
quality of life (QoL).13 (Although these late severe
toxicities are likely to affect fewer patients when con-
temporary RT delivery schedules are used.) Older
age, advanced T stage, larynx/hypopharynx primary
site and neck dissection after chemoradiotherapy all
increase the risk of severe late toxicity after chemora-
diotherapy and the additional benefit of chemotherapy
must be balanced against the risks for individual
patients. The benefit of chemotherapy decreases with
age and is non-significant above 70 years of age.
Thus, its use may be less appropriate in older patients.
Other systemic therapies that may be given concurrently
with RT include cetuximab, a monoclonal antibody
which competitively inhibits the cell-surface epidermal
growth factor receptor. Cetuximab has been shown to
improve locoregional control (three-year LRC 47 vs
34 per cent, p < 0.01) and overall survival (by 10 per
cent – three-year OS 55 vs 45 per cent) over RT alone
in a study of patients with locally advanced (stage III/
IV) head and neck cancer (27 per cent of whom had
laryngeal cancer). The benefit was maintained on
longer follow-up (five-year OS 46 vs 36 per cent).14
Toxicities of cetuximab include an acneiform rash and
hypersensitivity reactions but it does not increase the
rate of severe radiation-related mucositis. It is an alter-
native to concurrent chemoradiotherapy for patients
with laryngeal cancer who cannot receive concurrent
S79
chemoradiotherapy, as per the guidelines published in
2008 by the National Institute for Health and Care
Excellence (http://www.nice.org.uk/guidance/ta145).
Induction chemotherapy with cisplatin and 5-FU
(PF) prior to RT may also improve survival,15 but the
benefit of induction chemotherapy prior to standard
concurrent chemoradiotherapy schedules is currently
unproven. If induction chemotherapy is used, taxane
(docetaxel or paclitaxel) in combination with cisplatin
and 5-FU has been shown to be superior to PF
doublet chemotherapy in a meta-analysis of five rando-
mised trials.16
Radiotherapy may be used as a single modality where
comorbidity precludes the use of concurrent chemother-
apy, cetuximab or surgery. Conventional RT alone may
be suboptimal for the treatment of advanced laryngeal
cancer. Altered fractionation regimens (including accel-
eration and hyperfractionation) improve locoregional
control and overall survival compared with standard
fractionated RT for head and neck cancer patients who
elect or are selected to receive RT alone (albeit at the
cost of higher mucosal toxicity).17 However, altered
fractionation regimens do not appear to improve
outcome compared with or when combined with concur-
rent chemoradiotherapy which should be regarded as the
‘standard of care’ for the non-surgical management of
advanced laryngeal cancer. Accelerated fractionation
with hypoxia modification using either nimorazole or
carbogen/nicotinamide shows promising results and
requires further study. To that end, the UK clinical
trial NIMRAD (a randomised placebo-controlled trial
of synchronous NIMorazole vs RADiotherapy alone in
patients with locally advanced head and neck squamous
cell carcinoma not suitable for synchronous chemother-
apy or Cetuximab) (NCT01950689) is currently recruit-
ing in several UK centres.
It is important to note that, despite the laryngeal
preservation and survival rates conferred by non-surgi-
cal strategies, there is a dearth of robust data relating to
laryngeal function after chemoradiotherapy. By com-
parison with non-surgical treatments, any larynx-
preserving surgical procedure – TLM or partial open
procedure – undertaken for T2b/T3 carcinoma of the
larynx will result in dysphonia and prolonged swallow-
ing rehabilitation. Although most patients appear to
achieve satisfactory swallowing function eventually, a
small percentage of patients will require a total laryn-
gectomy for functional reasons.
Whilst TLM or partial open surgical procedures may
be considered as an alternative to non-surgical treatment
for selected cases in appropriate centres, laryngectomy
may be preferred for patients with significant pre-
existing laryngeal destruction by tumour and/or a pre-
treatment tracheostomy; however, reports of whether a
pre-treatment tracheostomy negatively affects outcome
after RT are conflicting and concurrent chemoradiother-
apy remains an option for these patients (25 per cent of
patients in the VALCSG study9 had a baseline tracheos-
tomy and they were not excluded from RTOG 91-11).
S80
Vocal cord fixation is not a contraindication to larynx
preservation (for either surgical or non-surgical modal-
ities), although it is likely that these patients will have
a poorer functional and oncological outcome than
patients with mobile vocal folds.
In the absence of clinical or radiological evidence of
nodal disease, elective treatment (RT or surgery ±
post-operative RT) is recommended to at least lymph
node levels II, III and IV bilaterally.
Recommendations
• Most patients with T2b–T3 glottic cancers are
suitable for non-surgical larynx preservation
therapies (R)
• Concurrent chemoradiotherapy should be
regarded as the standard of care for non-
surgical management (R)
• Subject to the availability of appropriate
surgical expertise and multi-disciplinary
rehabilitation services, TLM or open partial
surgical procedures ± post-operative RT, may
also be appropriate in selected cases (R)
• In the absence of clinical or radiological
evidence of nodal disease, elective treatment
(RT or surgery ± post-operative RT) is
recommended to at least lymph node levels II,
III and IV bilaterally. In node positive disease,
it is recommended that lymph node levels
II–V should be treated on the involved side. If
level II nodes are involved, then elective
irradiation of ipsilateral level Ib nodes may be
considered (R)
T3 supraglottic carcinoma
The principles of organ preservation for T3 supraglottic
cancers are the same as for glottic cancers. Tumour
size, pre-treatment laryngeal function and performance
status should direct the management of individual
patients. Rates of salvage laryngectomy after surgical
and non-surgical treatment of supraglottic cancers are
lower than for glottic cancers. Vocal cord function is
usually well preserved following TLM or supraglottic
laryngectomy; however, rehabilitation of swallowing
function following supraglottic surgery may be pro-
longed and, whilst most patients achieve satisfactory
swallowing function, this cannot be guaranteed.
T3 supraglottic cancers have a significantly higher
risk of nodal disease (occult and clinical) than glottic
tumours and this must be taken into account when con-
sidering how to manage the neck. In the absence of
clinical or radiological evidence of nodal disease, elect-
ive treatment – RT and/or selective neck dissection –
is recommended to at least lymph node levels II, III, IV
bilaterally.
There is general agreement that chemoradiotherapy
is sufficient to treat early nodal disease (N1, single
T M JONES, M DE, B FORAN et al.
lymph node <3 cm) in patients with glottic cancers.
Since publication of the last edition, management of
N2 (multiple lymph nodes and/or >3–6 cm) or N3
(>6 cm) nodal disease has been informed by the
PET-Neck clinical trial.18 The data confirm that posi-
tron emission tomography combined with computed
tomography (PET–CT) surveillance of the neck in che-
moradiotherapy complete responders, obviates the
need for an elective neck dissection in patients with a
negative PET–CT scan result.
Recommendations
• Most patients with T3 supraglottic cancers
are suitable for non-surgical larynx
preservation therapies (R)
• Concurrent chemoradiotherapy should be
regarded as the standard of care for non-
surgical management (R)
• Subject to the availability of appropriate
surgical expertise and multi-disciplinary
rehabilitation services, TLM or open partial
surgical procedures ± post-operative RT, may
also be appropriate in selected cases (R)
• In the absence of clinical or radiological
evidence of nodal disease, elective treatment
(RT or surgery ± post-operative RT) is
recommended to at least lymph node levels II,
III and IV bilaterally. In node positive disease,
lymph node levels II–V should be treated on
the involved side (R)
• As per the PET-Neck clinical trial, patients with
N2 or N3 neck disease who undergo treatment
with chemoradiotherapy to their laryngeal
primary and experience a complete response
with a subsequent negative post-treatment
PET–CT scan do not require planned neck
dissection. In contrast, patients who have a
partial response to treatment or have increased
uptake on a post-treatment PET–CT scan
should have a neck dissection (R)
T4 laryngeal carcinoma
Larynx preservation with chemoradiotherapy should be
considered for T4 tumours, unless there is tumour inva-
sion through cartilage into the soft tissues of the neck,
in which total laryngectomy followed by adjuvant treat-
ment yields better outcomes. The VALCSG study9
showed reduced tumour response to chemotherapy
and higher rates of salvage laryngectomy for T4
tumours (56 per cent for T4 vs 29 per cent for T3
tumours, p = 0.001). Nevertheless, larynx preservation
can be achieved in a significant proportion of patients
with T4 disease, without detriment to survival when
salvage laryngectomy is incorporated. However, once
again, few data are available correlating laryngeal
LARYNGEAL CANCER: UK GUIDELINES
preservation with function and QoL. Good patient
selection is of paramount importance. Patients with
large-volume T4 tumours – defined as extension of
tumour through thyroid cartilage or tumour extension
greater than 1 cm into the base of tongue – were
excluded from RTOG 91-1110 as they are poor candi-
dates for organ preservation. Patients with significant
pre-existing laryngeal destruction by tumour and/or a
pre-treatment tracheostomy may also be better suited
to a total laryngectomy. Total laryngectomy may
confer a better QoL than a preserved, but poorly func-
tioning, larynx.
Patients with large-volume T4 tumours who are
unsuitable for surgery because of inoperable (T4b)
disease have been treated with combined-modality
organ preservation therapy with significant rates of
disease control (71 per cent at four years) and overall
survival (56 per cent at four years) in retrospective
studies. Induction chemotherapy may be used to treat
large volume, symptomatic disease prior to commence-
ment of concurrent chemoradiotherapy.
Lymph node levels II–V bilaterally should be
treated, irrespective of the pre-treatment clinical nodal
status. As per the findings of the PET-Neck trial18
(see above), a planned neck dissection is not necessary
in patients who experience a complete response to che-
moradiotherapy and have a post-treatment negative
PET–CT scan. Improved systemic therapies and RT
dose intensification using IMRT may improve out-
comes for this patient group in future.
Recommendations
• Larynx preservation with concurrent
chemoradiotherapy should be considered for
T4 tumours, unless there is tumour invasion
through cartilage into the soft tissues of the
neck, in which case total laryngectomy yields
better outcomes (R)
• In the absence of clinical or radiological
evidence of nodal disease, elective treatment
(RT or surgery ± post-operative RT) is
recommended to bilateral lymph node levels
II, III, IV, V and VI (R)
Post-operative RT /chemoradiotherapy
Radiotherapy delivered post-operatively to the primary
site and/or neck in patients at high risk of locoregional
recurrence can improve locoregional control and sur-
vival. Post-operative RT is recommended for pT4 laryn-
geal cancers of any nodal stage, pT1/T2/T3 tumours
with N2–N3 nodal stage and for all patients with close
or positive resection margins and/or extracapsular
spread; other unfavourable pathological factors, includ-
ing peri-neurial and vascular invasion, are relative indica-
tions for post-operative RT. Administration of concurrent
cisplatin chemotherapy with post-operative RT improves
S81
locoregional control and disease-free survival compared
with post-operative RT alone for locally advanced
tumours,19,20 albeit at the expense of increased mucosal
and haematological toxicity and possibly increased
deaths. This approach improves overall survival in
selected patients, particularly with extracapsular spread
and/or positive margins, and should be used selectively
for patients at highest risk of relapse.
Key points
• Approximately 2400 patients are diagnosed with
laryngeal squamous cell carcinoma and ∼800
patients die of the disease per annum in the UK
• Early stage tumours of the glottis present with
hoarseness, whilst tumours of the supraglottis and
more advanced glottic tumours may present with
pain, odynophagia and/or dysphagia, a neck lump
or even airway compromise
• Meticulous endoscopic inspection of the tumour
under general anaesthetic and imaging of the head,
neck and thorax is needed for staging
• Radiotherapy and transoral laser microsurgery are
reasonable treatment options for T1a–T2a glottic
and T1–T2 supraglottic carcinomas
• Most patients with T2b–T3 glottic and T3 supraglot-
tic cancers are suitable for non-surgical larynx pres-
ervation therapies. Transoral laser microsurgery or
open partial surgical procedures ± post-operative
radiotherapy may be also be appropriate in selected
cases
• Concurrent chemoradiotherapy should be regarded
as standard of care for the non-surgical management
of stage III/IV laryngeal cancer
• Patients with N2 or N3 neck disease who experience a
complete response with a subsequent negative post-
treatment PET–CT scan do not require planned
neck dissection
• Post-operative (chemo)radiotherapy is recommended
in the presence of advanced disease or adverse histo-
logical features.
References
1 Rachet B, Quinn MJ, Cooper N, Coleman MP. Survival from
cancer of the larynx in England and Wales up to 2001. Br J
Cancer 2008;99(Suppl 1):S35–7
2 Upile NS, Shaw RJ, Jones TM, Goodyear P, Liloglou T, Risk
JM et al. Squamous cell carcinoma of the head and neck
outside the oropharynx is rarely human papillomavirus related.
Laryngoscope 2014;124:2739–44
3 Dey P, Arnold D, Wight R, MacKenzie K, Kelly C, Wilson J.
Radiotherapy versus open surgery versus endolaryngeal
surgery (with or without laser) for early laryngeal squamous
cell cancer. Cochrane Database Syst Rev 2002;CD002027
4 Steiner W, Ambrosch P, Rodel RM, Kron M. Impact of anterior
commissure involvement on local control of early glottic carcin-
oma treated by laser microresection. Laryngoscope 2004;114:
1485–91
5 Gowda RV, Henk JM, Mais KL, Sykes AJ, Swindell R, Slevin
NJ. Three weeks radiotherapy for T1 glottic cancer: the Christie
and Royal Marsden Hospital Experience. Radiother Oncol
2003;68:105–11
6 Thomas LD, Basavaiah M, Mehanna N, Jones H, Paleri V. Open
Conservation partial Laryngectomy for laryngeal cancer: a
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Systematic review of English language literature. Cancer Treat
Rev 2012;38:203–11.
7 Paleri V, Thomas L, Basavaiah N, Drinnan M, Mehanna H,
Jones T. Oncologic outcomes of open conservation laryngect-
omy for radiorecurrent laryngeal carcinoma: a systematic
review and meta-analysis of English-language literature.
Cancer 2011;117:2668–76
8 Ambrosch P. The role of laser microsurgery in the treatment of
laryngeal cancer. Curr Opin Otolaryngol Head Neck Surg 2007;
15:82–8
9 The Department of Veterans Affairs Laryngeal Cancer Study
Group. Induction chemotherapy plus radiation compared with
surgery plus radiation in patients with advanced laryngeal
cancer. N Engl J Med 1991;324:1685–90
10 Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R,
Morrison W et al. Concurrent chemotherapy and radiotherapy
for organ preservation in advanced laryngeal cancer. N Engl J
Med 2003;349:2091–8
11 Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H,
Pajak TF et al. Long-term results of RTOG 91-11: a comparison
of three nonsurgical treatment strategies to preserve the larynx in
patients with locally advanced larynx cancer. J Clin Oncol 2013;
31:845–52
12 Pignon JP, le Maitre A, Maillard E, Bourhis J. Meta-analysis of
chemotherapy in head and neck cancer (MACH-NC): an update
on 93 randomised trials and 17,346 patients. Radiother Oncol
2009;92:4–14
13 Machtay M, Moughan J, Trotti A, Garden AS, Weber RS,
Cooper JS et al. Factors associated with severe late toxicity
after concurrent chemoradiation for locally advanced head and
neck cancer: an RTOG analysis. J Clin Oncol 2008;26:3582–9
14 Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK
et al. Radiotherapy plus cetuximab for locoregionally advanced
head and neck cancer: 5-year survival data from a phase 3 ran-
domised trial, and relation between cetuximab-induced rash and
survival. Lancet Oncol 2010;11:21–8
T M JONES, M DE, B FORAN et al.
15 Monnerat C, Faivre S, Temam S, Bourhis J, Raymond E. End
points for new agents in induction chemotherapy for locally
advanced head and neck cancers. Ann Oncol 2002;13:995–1006
16 Blanchard P, Bourhis J, Lacas B, Posner MR, Vermorken JB,
Hernandez JJ et al. Taxane-cisplatin-fluorouracil as induction
chemotherapy in locally advanced head and neck cancers: an
individual patient data meta-analysis of the meta-analysis of
chemotherapy in head and neck cancer group. J Clin Oncol
2013;31:2854–60
17 Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J
et al. Hyperfractionated or accelerated radiotherapy in head and
neck cancer: a meta-analysis. Lancet 2006;368:843–54
18 Mehanna H, Wong WL, McConkey CC, Rahman J, Robinson M,
Hartley A et al. PETCT surveillance versus neck dissection in
advanced head and neck cancer. N Engl J Med 2016;374:
1444–54.
19 Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre
JL, Greiner RH et al. Postoperative irradiation with or without
concomitant chemotherapy for locally advanced head and
neck cancer. N Engl J Med 2004;350:1945–52
20 Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH,
Saxman SB et al. Postoperative concurrent radiotherapy and
chemotherapy for high-risk squamous-cell carcinoma of the
head and neck. N Engl J Med 2004;350:1937–44
Address for correspondence:
Terence M. Jones,
Department of Molecular and Clinical Cancer Medicine,
University of Liverpool, Aintree University Hospitals
NHS Foundation Trust,
Liverpool, UK.
E-mail: t.m.jones@liverpool.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S83–S89. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000499

Oral cavity and lip cancer: United Kingdom National

Multidisciplinary Guidelines

C KERAWALA1, T ROQUES2, J-P JEANNON3, B BISASE4

1
Head and Neck Unit, The Royal Marsden Hospital, London, 2Norfolk and Norwich University Hospitals NHS
Foundation Trust, Norwich, 3Department of Otolaryngology-Head and Neck Surgery, Guy’s and St Thomas’ NHS
Foundation Hospital Trust, King’s College, London, and 4Queen Victoria Hospital, East Grinstead, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. It provides recommendations on the assessment and management of patients with cancer of
the oral cavity and the lip.

Recommendations
• Surgery remains the mainstay of management for oral cavity tumours. (R)
• Tumour resection should be performed with a clinical clearance of 1 cm vital structures permitting. (R)
• Elective neck treatment should be offered for all oral cavity tumours. (R)
• Adjuvant radiochemotherapy in the presence of advanced neck disease or positive margins improves control
rates. (R)
• Early stage lip cancer can be treated equally well by surgery or radiation therapy. (R)

Introduction to carcinogens such as tobacco or alcohol is thought

In order of decreasing frequency, malignant tumours of
the oral cavity affect the anterior two-thirds of the
tongue, floor of mouth, buccal mucosa, retromolar
trigone, hard palate and gingivae. Tumours of the lip
require separate consideration as their natural history
differs from oral cavity disease. The overwhelming
majority of oral cavity cancers are squamous cell car-
cinomas (SCCs). Non-squamous cell tumours are pre-
dominantly of salivary gland origin and are discussed
elsewhere in these guidelines. The heterogeneous
nature of oral cavity tumours, the functional and cos-
metic sequelae of their management and the frequent
medical co-morbidities that co-exist in this patient
group demand that treatment options should be consid-
ered by a multidisciplinary team before reaching a final
plan through consensus with the patient and carers. The
overall treatment intention, whether curative or pallia-
tive, should be clearly communicated at the outset.
Pathology
Oral cavity
Carcinoma of the oral cavity may develop de novo or
from a pre-malignant dysplastic lesion that appears
clinically as leukoplakia, erythroplakia or a combin-
ation of the two. In both instances, chronic exposure
to be important. Carcinogenesis is a multistep process
that involves over expression of oncogenes and inacti-
vation of tumour suppressor genes. The p53 suppressor
gene has been identified as being important in oral
cavity carcinomas in smokers. The presence of
human papilloma virus (HPV) that expresses the p16
oncoprotein in oral cavity carcinoma in non-smokers
is of significant importance as the cancers tend to
occur in younger patients. However, HPV-related
disease does not appear as frequently in the oral
cavity as it does in the oropharynx and appears not to
proffer as much of an improvement in prognosis.1
The importance of epidermal growth factor receptor
(EGFR) status in oral cavity carcinoma remains
unclear. Whilst over expression does appear to be
related to poor prognosis, EGFR status does not yet
appear to be correlated with response to targeted
molecular therapies such as cetuximab.
Within the diagnosis of oral cavity SCC, several
histological subtypes exist with different prognoses
such as verrucous (better prognosis) and basaloid
(worse prognosis) carcinomas. Oral SCCs are classified
according to grade depending on several histopatho-
logical features such as degree of keratinisation,
nuclear pleomorphism, cellular atypia and mitotic
activity. They are divided into well, moderate and
S84
poorly differentiated carcinomas. However, tumour
grade is of limited prognostic value due to the hetero-
geneity within a tumour and sampling error. Several
other histopathological factors have been shown to be
of prognostic importance such as tumour thickness,
extra-capsular spread (ECS) of nodal metastasis2 and
patterns of invasion. Oral tongue SCC of greater than
4 mm tumour thickness is considered to represent a
>20 per cent risk of cervical lymph node metastatic
involvement.3 Extra-capsular spread in cervical
lymph nodes is consistently associated with an
increased risk of local regional recurrence, distant
metastasis and decreased survival. The pattern of
invasion in oral SCC appears to be important in deter-
mining prognosis in that those cancers that have a non-
cohesive invasive front and/or peri-neurial invasion
appear to be associated with an increased risk of
loco-regional relapse.4 These pathological factors
therefore supplement the tumour–node–metastasis
classification and are now incorporated in pathological
datasets.
Lip
Cancer of the lip is the most common malignant tumour
affecting the head and neck. Its clinical behaviour is
similar to that of skin cancer. Incidence rates are
around 13.5 per 100 000 in Oceania, 12 per 100 000
in Europe and 12.7 per 100 000 in North America.5
The factors commonly cited as important in lip
cancer are solar radiation, tobacco smoking and
viruses. About 90 per cent of tumours arise in the
lower lip with 7 per cent occurring in the upper lip
and 3 per cent at the oral commissure.
Squamous cell carcinoma is the commonest histo-
logical tumour type in lip cancers, followed by basal
cell carcinoma. The most common non-mucosal form
of lip cancer arises from tumours of the minor salivary
glands, with in converse to mucosal lip cancer the
upper lip being more commonly involved than the
lower.
Clinical presentation
The majority of SCCs (>95 per cent) of the oral cavity
are presented as ulcers or masses. Early lesions can be
subtle and appear as flat, discoloured areas (leukoplakia
TABLE I
T STAGING FOR ORAL CAVITY TUMOURS
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tis Carcinoma in situ
T1 Tumour 2 cm or smaller in greatest dimension
T2 Tumour larger than 2 cm but 4 cm or smaller in greatest
dimension
T3 Tumour larger than 4 cm in greatest dimension
T4a Tumour invades the larynx, deep/extrinsic muscle of
tongue, medial pterygoid, hard palate or mandible
T4b Tumour invades lateral pterygoid muscle, pterygoid plates,
lateral nasopharynx or skull base or encases carotid
artery
C KERAWALA, T ROQUES, J-P JEANNON et al.
or erythroplakia).6 A non-healing ulcer is the most
common presentation. Advanced tumours can present
with invasion of neighbouring structures causing
tooth mobility, trismus, sensory change, referred
otalgia and neck masses. The clinical presentation of
cancer of the lip is usually that of an exophytic,
crusted lesion with variable invasion into underlying
muscle (related to the size of the primary tumour).
The adjacent lip often shows features of actinic sun
damage such as colour change, mucosal thinning and
various associated areas of leukoplakia.7
Assessment and staging
Clinical examination
Clinical examination is useful in identifying new
tumours and for surveillance after treatment. Given
its importance in diagnosis and treatment planning, a
systematic approach must be adopted to include the
primary site and neck, with assessment of the index
tumour size as well as any potential invasion of local
structures. The examination should be preceded by a
focused history to elucidate any potential co-morbid-
ities and social circumstances that may influence the
choice of treatment.
Imaging considerations
Imaging of early stage tumours of the lip is usually not
indicated. However, advanced tumours of the lip (par-
ticularly if they are adherent to the adjacent mandible)
require computed tomography (CT) or magnetic reson-
ance imaging to allow complete staging and treatment
planning with regard to resection margins which may
of necessity include adjacent bone.
Oral cavity tumours are almost always staged with
cross-sectional imaging to include the chest where the
demonstration of simultaneous pulmonary parenchy-
mal disease may influence curability.8,9 Sentinel node
lymph node biopsy has been shown to be an effective
method of assessment of the neck in early stage oral
cancers.10
Pre-treatment staging
Staging of primary cancer of the lip and oral cavity is
similar and shown in Table I. T4 tumours of the lip
usually only invade the anterior mandible or maxilla
rather than other structures.
Management
Oral cavity
Although there is no randomised data exclusively com-
paring the different treatment modalities available in
the management of oral cavity cancer, non-surgical
clinical trials often present this subsite in combination
with others in the head and neck. Two-year crude sur-
vival rates are around 85 per cent for stage I disease, 70
per cent for stage II disease11, 50 per cent for stage III
disease and 40 per cent for stage IV disease.12
ORAL CAVITY AND LIP CANCER: UK GUIDELINES
General principles
Surgery. Factors such as fitness for anaesthesia, pre-
vious cancer treatment and patient choice as well as the
skill mix and resources available to the treating team
must be considered.13,14 There are a number of
different options available under the broad banner of
surgery: conventional surgery, laser surgery, thermal
surgery and photodynamic therapy (PDT).15 Curative
surgery for cancer of the oral cavity involves resection
of tumour with an appropriate safety margin and subse-
quent reconstruction of the tissues in order to maintain
function. The size and location of the primary tumour
determine the need or otherwise for adjuncts such as
temporary tracheostomy and access procedures. Many
tumours in the anterior aspect of the oral cavity can
be accessed via the transoral route. This is ideal,
since in so doing the circumferential muscular sphinc-
ter is maintained and scars avoided. However, as
tumours increase in size and become more posteriorly
placed, a controlled resection may only be possible
by performing either a lingual release or resorting
to lip-split and mandibulotomy. There are several
options for the lip skin incision with some form of Z-
plasty being desirable to both disguise and lengthen
the scar, thus preventing post-operative wound contrac-
tion and distortion to the vermilion border.
Effective tumour ablation is achieved by ensuring
good visibility which in turn is dependent on appropri-
ate access. In order to maximise the chances of achiev-
ing complete tumour resection with a clear margin of
normal tissue, both visual inspection and palpation
must be employed. The method of ablation, be it
scalpel, laser, diathermy or coblation, is a matter of per-
sonal preference. For small, superficial lesions laser
vaporisation may be employed although this often
does not permit accurate histological assessment of
the adequacy of resection and so may compromise
decisions surrounding the need or otherwise for
adjuvant treatments. Lasers and thermal techniques,
whilst reducing the amount of intra-operative bleeding,
can cause histological artefact and morphological
distortion of tissue margins. Coblation involves the
generation of bipolar radio-frequency waves. Tissue
temperatures of around 60 °C ensue, much lower than
temperatures generated by conventional diathermy.
Although this is claimed to reduce post-operative
pain, the technique has been associated with increased
levels of haemorrhage in certain head and neck sites.
The primary aim of surgery in oral cavity cancer is
tumour resection with a clinical clearance of ideally
1 cm (vital structures permitting). ‘Close’ margins
(defined as a histopathological margin of less than
5 mm) mean further surgery or adjuvant radiotherapy
(RT) and should be discussed by the multidisciplinary
team. The use of intra-operative frozen sections to
assist marginal clearance is controversial.16 Although
the accuracy is good in histological terms, they can
give a false sense of security and invariably prolong
S85
operative time. Adoption of a Mohs-type technique
where the whole of the resection bed is mapped out
is impractical given the size of the average intra-oral
resection. Intra-operative tumour tissue marking has
been attempted with agents such as toluidine-blue but
this has limited value in marginal clearance because
of high false positive rates.17 Where bony resection is
required, the assessment is largely based upon clinical
and radiological findings.18 Intra-operative techniques
such as periosteal stripping however remain reliable.
Frozen section of cancellous bone can be used to
guide the extent of the resection.
Cervical lymphadenectomy in the form of elective
neck dissection offers improved overall and disease-
free survival compared with therapeutic neck dissec-
tion for the majority of oral cancers with recent
evidence suggesting advantages even for tumours less
than 4 mm in thickness.19 Sentinel node lymph node
biopsy may be indicated for small (T1 and T2)
cancers since a negative sentinel node biopsy can
avoid the morbidity of neck dissection and may be
more cost-effective.10
Recommendations
• Surgery remains the mainstay of management
for oral cavity tumours (R)
• Tumour resection should be performed with a
clinical clearance of 1 cm vital structures
permitting (R)
• Elective neck treatment should be offered for
all oral cavity tumours (R)
Radiotherapy ± chemotherapy. In the oral cavity,
primary radiochemotherapy is less commonly utilised
than other head and neck sites. However, it should be
considered in selected patients. Concurrent radioche-
motherapy combines platinum-based chemotherapy
with external beam radiotherapy (EBRT) to 70 Gy.
While the most recognised concurrent chemotherapy
regimen is cisplatin 100 mg/m2 three weekly,
varying doses and schedules are acceptable practice,
as is substitution by carboplatin. Patients undergoing
radiochemotherapy require speech, swallow and
dietetic support, in both the acute and long-term
setting. Patients who are excluded from platinum-
based chemotherapy may be considered for EBRT
with cetuximab under National Institute for Health
and Care Excellence guidance. Neo-adjuvant chemo-
therapy with taxanes, cisplatin and 5-fluro-uracil
(TPF) is a potent combination in advanced, inoperable
disease in fit patients, if followed by concurrent
radiochemotherapy.
External beam radiotherapy is not usually recom-
mended as the primary curative treatment in oral
cavity tumours because the significant morbidity of
S86
treatment limits radiation dose and therefore cure
rates. Severe mucositis of the treated volume during
and immediately after treatment is inevitable and
will affect function and nutrition. Long-term pain is
a common sequelae if high enough radiation doses
to cure primary tumours are used while osteoradione-
crosis of the mandible is a particular risk when
irradiating the oral cavity. External beam radiother-
apy alone can be used to treat the neck prophylactic-
ally after excision of a small primary without a neck
dissection. Brachytherapy as sole treatment or as a
boost after EBRT can produce cure rates equivalent
to those in surgical series. As the radiation dose is
concentrated in the tumour tissue more effectively
than with EBRT, higher doses and fewer long-term
side effects can be achieved. Brachytherapy requires
specific expertise which is not widely available in the
UK.
Adjuvant RT improves local control and overall sur-
vival when added to surgery in locally advanced
cancers. It should be considered in all patients with
larger T3 or T4 tumours, where there is ECS or
N2–3 neck disease. Other poor prognostic factors
such as grade or peri-neurial invasion may also
inform the decision.4 The morbidity of radiation to
the primary site in the oral cavity means the benefits
and side effects should be carefully considered with
each individual patient.
Concomitant chemotherapy improves the effective-
ness of adjuvant RT – more so in oral cavity tumours
than in other primary sites of the upper aerodigestive
tract – and should always be considered in patients
over 71 years old with relevant histological features
when RT is discussed.20 However, it increases the
acute and late morbidity of treatment. In patients with
incurable disease, a short course of palliative RT may
help to improve local symptoms. Palliative chemother-
apy with platinum-based drugs and 5FU or capecita-
bine can also be considered to help symptoms and
improve survival.
Early stage cancer. Early stage tumours (T1 and small
T2) can be adequately treated with either surgery or
brachytherapy. Treatment choice may be influenced
by tumour size, location, depth of invasion, proximity
to bone, growth patterns including differentiation,
neck nodal disease and access to services.
Advanced stage cancer. For advanced disease, stages III
and IV (T3, T4 N0 and T1–4 N1), traditional manage-
ment includes surgical resection, neck dissection,
reconstruction and post-operative RT. The latter
should be offered to at least 60 Gy equivalent and opti-
mally start within 6 weeks of surgery. In fit patients
under the age of 71, adjuvant radiochemotherapy up
to 66 Gy with concurrent platinum-based chemother-
apy should be considered for those with positive surgi-
cal margins and/or ECS.21
C KERAWALA, T ROQUES, J-P JEANNON et al.
Recommendation
• Adjuvant radiochemotherapy in the presence
of advanced neck disease or positive margins
improves control rates (R)
Recurrent cancer. Patients with locally recurrent disease
should be fully restaged and assessed for consideration
of curative treatment in the form of repeat surgery, pos-
sible EBRT or brachytherapy if available. Palliative RT
may be used, either over short fractionation schedules
or split course, for patients with advanced and inoper-
able disease, or those who are not fit for a more toxic,
radical approach. Palliative chemotherapy should be
considered for inoperable, recurrent and or metastatic
disease, when possible patients should be offered
entry to clinical trials.
Reconstruction following surgical ablation of oral cavity
tumours. There is a plethora of retrospective series
reporting technique and outcome of a wide range of
reconstructive techniques for the repair of defects
following ablation for oral cavity tumours.22,23
However, there are no randomised controlled trials.
The literature suffers from a wide range of heteroge-
neous factors introducing bias including tumour sites,
stages, patient variables, operators, surgical techniques,
study designs, small numbers, lack of clarity for treat-
ment intention and the reporting of different outcome
measures.
Reconstructive options include local flaps, regional
pedicled flaps and microvascular free tissue transfer
discussed elsewhere in the guidelines.24 Hard tissues
may be reconstructed using free autologous bone
grafts but more commonly involve the use of free
tissue transfer from iliac crest, fibula, radius or scapula.
Lip
General principles. Early stage cancer can be treated
equally well by surgery or radiation therapy. The
five-year crude survival rates for surgical treatment
are about 75–80 per cent for T1 to T2 tumours, drop-
ping to 40–50 per cent for T3 and T4 tumours. The
primary lymphatic drainage of the lower lip is to sub-
mental and submandibular level cervical lymph
nodes. Neck dissection is generally not performed in
the absence of clinically suspicious cervical lymph
nodes as more than 5 per cent of patients are likely to
develop recurrence in the neck following treatment of
the primary lesion. The presence of cervical nodes at
presentation is a poor prognostic indicator. Small
lesions are managed by simple surgical excision and
primary closure. Equally good results can be achieved
with fractionated EBRT or brachytherapy. External
beam radiotherapy using electrons or orthovoltage
photons minimises dose to the oral cavity so that muco-
sitis occurs only on the treated lip.
ORAL CAVITY AND LIP CANCER: UK GUIDELINES
Larger lesions of the lip require more consideration
with regard to reconstruction techniques. The function-
al outcome of the repair with regard to lip sensitivity
and muscle function also needs to be taken into consid-
eration. Whenever possible full thickness skin flaps
(skin, muscle and mucosa) should be used. The repair
should provide sufficient mucosa contiguous to the
commissure to avoid contracture. Superficial field
change lesions affecting the external vermilion of the
lip such as leukoplakia or actinic keratosis are best
managed via a lip shave and mucosal advancement.
Various studies have shown that for small tumours
radiation therapy can achieve a cure rate equivalent
to that obtained surgically. However, the cosmetic
results of EBRT to the lip are usually not as satisfactory
as surgical excision and repair. Surgical excision of
small lip tumours involves relatively minor surgery,
often under local anaesthetic and may be therefore
less burdensome for the patient than a course of RT.
The lower lip is one of the few ideal sites for orthovol-
tage therapy. Using a single anterior field a fractionated
course of 50 Gy in 15 fractions over 3 weeks is admi-
nistered. Brachytherapy can produce good aesthetic
results but is not widely available in the UK.
Iridium192 can be used in the treatment of lip cancer.
Patients can be treated twice a day for 4–5 days with
a total radiation dose between 40 and 45 Gy in 8–10
fractions.
Lower lip. Small lesions invading into the adjacent
muscle are amenable to a wedge excision. The excision
can also be completed using a ‘W’ plasty or half ‘W’
plasty to avoid the inferior aspect of the excision
encroaching on the crease line of the chin. If the dimen-
sions of the lip resection require the introduction of
tissue to minimise functional problems and microsto-
mia, then this may be by means of Abbe, Abbe-
Estlander or Karapandzic flaps. The Estlander modifi-
cation of the cross-lip flap is used to reconstruct the
oral commissure. The Karapandzic flap is useful for
defects involving more than two-thirds of the lower
lip, where the defect is in the midline. The main advan-
tage of the Karapandzic flap is that the nerve and blood
supply is retained and the underlying orbicularis
muscle rotated so that a sensate functional lip recon-
struction results. The various reconstructive options
are identified in Table II. With larger defects of the
TABLE II
RECONSTRUCTIVE OPTIONS FOR LOWER LIP DEFECTS
Defect size Procedure
<1/2 Wedge excision
1/2 to 2/3 Karapandzic flap
Abbe-Estlander flap
>2/3 Bernard Burow
Gillies fan flap
Webster flap
Free flap
S87
lower lip reconstruction requires either large cheek
flaps to be advanced to repair the defect or the use of
free tissue transfer. The common forms of cheek flap
include the bilateral Gillies fan flaps or the
Bernard–Webster cheek flap reconstruction. Free
tissue transfer is required for lip reconstruction when
the total remaining lip or adjacent rotated tissue is
insufficient to create a reasonable circular stoma.
Recommendation
• Early stage lip cancer can be treated equally
well by surgery or radiation therapy (R)
Upper lip. Similar to lower lip defects wedge excisions
and advancement flaps can address upper lip defects
which involve up to one half of the width of the
upper lip. Care should be taken to respect the relevant
aesthetic subunits. Defects of less than a third in the
midline can be closed primarily. Defects involving
greater than half of the lip can be reconstructed with
cross-lip flaps from the lower lip. Peri-alar crescentic
advancement flaps can be used to disguise the advance-
ment of the upper lip when the advancement
encroaches to the medial part of the nose. For defects
involving more than two-thirds of the lip, a Burow-
Diffenbach reconstruction can be performed. This
flap replaces upper lip defects by utilisation of laterally
based advancement flaps. Bilateral peri-alar crescentic
excisions are required to provide adequate advance-
ment. The various reconstructive options are identified
in Table III.
Most large series in the literature show that the
majority of patients have small lesions without palpable
cervical metastases although the incidence of syn-
chronous cervical metastases increases as the size of
the primary tumour increases. The local recurrence
rate is low due to the relative ease of surgical excision.
Even re-excision because of local failure leads to
salvage in 75–80 per cent of cases.
Developing therapeutic regimens
Neoadjuvant chemotherapy with TPF followed by
surgery and then RT is accruing evidence in other
primary sites. Radio chemotherapy with the addition
TABLE III
RECONSTRUCTIVE OPTIONS FOR UPPER LIP DEFECTS
Defect size Procedure
<1/2 Wedge excision
1/2–2/3 Peri-alar crescentic flap
Reverse Karapandzic flap
Abbe–Estlander flap
>2/3 Burow–Diffenbach flap
Free flap
S88
of targeted agents requires further evaluation.
Radiotherapy alone vs RT plus cetuximab in intermedi-
ate cancers and the use of positron emission tomogra-
phy–computed tomography to define the gross
tumour volume and to assess response to non-surgical
treatments is the subject of ongoing research. Agents
such as palifermin and amifostine are under investiga-
tion to reduce radiation toxicity but are not yet in
routine use. Molecular mapping to determine the indi-
vidualised, sub-clinical spread to inform the clinical
target volume requires further evaluation. Likewise
further work is required to establish the long-term
quality of life, toxicity recognition, management and
support in head and neck cancer patients receiving
radiochemotherapy.
Xerostomia is one of the most unpleasant permanent
complications from RT of the oral cavity. Sparing of
the salivary glands by intensity-modulated radiation
therapy may improve toxicity without reduction in
local control.
The efficacy of hyperbaric oxygen in the prevention
of osteoradionecrosis remains unproven, as does the
use of medical therapies such as pentoxifylline and toc-
opherol in established cases.
Photodynamic therapy has been advocated as a tech-
nique which causes selective tumour destruction by cell
apoptosis. Advocates suggest minimal scarring and pres-
ervation of uninvolved tissue thereby minimising any
functional deficit caused by tumour ablation.
Unfortunately the photograph-sensitising agents current-
ly available are insufficiently selective to prevent normal
tissue damage and patients must be protected from
exposure to sunlight for several days. Since the wound
sloughs and heals by secondary intention, there is little
benefit in functional terms of PDT over the more trad-
itional techniques. Foscan® mediated PDT can also be
used to treat primary cancer of the lip, where treatment
yields complete response rates comparable with those
published for surgery or RT. The lack of tissue
memory for PDT means that unlike RT this treatment
can be repeated on a number of occasions.
Key points
• The majority of malignant tumours of the oral cavity
are squamous cell carcinomas
• The clinical behaviour of lip cancer is akin to skin
cancer
• While tobacco and alcohol are the main carcinogens
implicated in oral cavity cancer, a small but signifi-
cant role for human papilloma virus is recognised
• Surgical resection is the primary modality used to
manage most oral cancers
• Elective neck management is indicated for any
tumour when the risk of occult nodal involvement
is >20 per cent
• Several reconstructive options exist to repair soft
tissue and bony defects after tumour resection
• Tumour thickness, positive margins and extra-capsu-
lar spread of nodal metastasis and pattern of invasion
C KERAWALA, T ROQUES, J-P JEANNON et al.
have been shown to have significant prognostic
value
• Post-operative adjuvant radiation or radiochemother-
apy should be considered in the presence of
unfavourable disease factors.
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© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000505

Oropharyngeal cancer: United Kingdom National

Multidisciplinary Guidelines

H MEHANNA1, M EVANS2, M BEASLEY3, S CHATTERJEE4, M DILKES5, J HOMER6,

J O’HARA7, M ROBINSON8, R SHAW9, P SLOAN10
1
Institute of Head and Neck Studies and Education, University of Birmingham, Birmingham, 2Velindre Cancer
Centre, Cardiff, 3Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust,
Bristol, 4Tata Medical Center, Kolkata, India; Newcastle University, Newcastle upon Tyne, 5ENT Department,
Barts and The London NHS Trust, London, 6Department of Otolaryngology-Head and Neck Surgery, Manchester
Royal Infirmary and Christie Hospital, University of Manchester, Manchester, 7Department of Otolaryngology,
The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, 8School of Dental Sciences,
Newcastle University, Newcastle upon Tyne, 9Department of Molecular and Clinical Cancer Medicine, Liverpool
CR-UK Centre, Institute of Translational Medicine, University of Liverpool, Aintree University Hospitals NHS
Foundation Trust, Liverpool, and 10Department of Cellular Pathology, The Newcastle upon Tyne Hospitals NHS
Foundation Trust, Oral Health Research Group, Newcastle University, Newcastle upon Tyne, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. There has been significant debate in the management of oropharyngeal cancer in the last
decade, especially in light of the increased incidence, clarity on the role of the human papilloma virus in this
disease and the treatment responsiveness of the human papilloma virus positive cancers. This paper discusses
the evidence base pertaining to the management of oropharyngeal cancer and provides recommendations on
management for this group of patients receiving cancer care.
Recommendations
• Cross-sectional imaging is required in all cases to complete assessment and staging. (R)
• Magnetic resonance imaging is recommended for primary site and computed tomography scan for neck and
chest. (R)
• Positron emission tomography combined with computed tomography scanning is recommended for the
assessment of response after chemoradiotherapy, and has a role in assessing recurrence. (R)
• Examination under anaesthetic is strongly recommended, but not mandatory. (R)
• Histological diagnosis is mandatory in most cases, especially for patients receiving treatment with curative
intent. (R)
• Oropharyngeal carcinoma histopathology reports should be prepared according to The Royal College of
Pathologists Guidelines. (G)
• Human papilloma virus (HPV) testing should be carried out for all oropharyngeal squamous cell carcinomas as
recommended in The Royal College of Pathologists Guidelines. (R)
• Human papilloma virus testing for oropharyngeal cancer should be performed within a diagnostic service where
the laboratory procedures and reporting standards are quality assured. (G)
• Treatment options for T1–T2 N0 oropharyngeal squamous cell carcinoma include radical radiotherapy or
transoral surgery and neck dissection (with post-operative (chemo)radiotherapy if there are adverse
pathological features on histological examination). (R)
• Transoral surgery is preferable to open techniques and is associated with good functional outcomes in
retrospective series. (R)
• If treated surgically, neck dissection should include levels II–IV and possibly level I. Level IIb can be omitted if
there is no disease in level IIa. (R)
• If treated with radiotherapy, levels II–IV should be included, and possibly level Ib in selected cases. (R)
• Altering the modalities of treatment according to HPV status is currently controversial and should be
undertaken only in clinical trials. (R)
• Where possible, patients should be offered the opportunity to enrol in clinical trials in the field. (G)
OROPHARYNGEAL CANCER: UK GUIDELINES
Introduction and epidemiology
The incidence of oropharyngeal squamous cell carcin-
oma (OPSCC) is increasing significantly in developed
countries.1 In the USA, the incidence increased by 22
per cent from 1.53 per 100 000 to 1.87 per 100 000
between 1999 and 2006, after showing no change
between 1975 and 1999. The UK has seen a doubling
of incidence between 1990 and 2006. There has been a
further doubling in incidence between 2006 and 2010.
The increasing incidence of OPSCC is due to human
papilloma virus (HPV) infection, with HPV-16 being
the predominant subtype responsible. The proportion
of cases with evidence of HPV infection has risen
rapidly and HPV is now responsible for over 70 per
cent of OPSCCs in Europe and the USA.1,2 The rise
in HPV-related OPSCC has been called an ‘epidemic’
and is expected to continue.
Clinical presentation
Patients often present with a painless neck lump, with
few other symptoms. They may also complain of a
sore throat or tongue, otalgia, pain and/or difficulty
swallowing and/or a change in voice quality (hot
potato voice).
Assessment and staging
Clinical examination
Flexible direct endoscopy of the upper aerodigestive
tract is now available in virtually all ear, nose and
throat clinics in the UK. It is vital for assessing the
limits of spread, such as direct through and through
invasion of the soft palate from anterior to posterior
surfaces, the inferior extent of lateral pharyngeal wall
tumours into the vallecula and pyriform fossa, and
the superior extension of tonsillar cancers into the post-
nasal space and skull base.
Imaging considerations
Cross-sectional imaging is required in all cases to com-
plete assessment and staging. Magnetic resonance
imaging (MRI) scanning with contrast is optimal for
staging the primary tumour, particularly when asses-
sing soft tissue spread, such as in the tongue base
and/or body of the tongue.3,4 Computed tomography
(CT) scanning may also be required, particularly to
assess the extent of nodal disease and bony invasion,
e.g. body of the mandible and skull base in tonsillar
tumours and cervical spine in posterior pharyngeal
wall tumours.
The presence of nodal metastases should be evalu-
ated by CT or MRI in all patients. Ultrasound with or
without needle biopsy should be carried out for all
patients presenting with a neck lump and is an accur-
ate method of staging nodal disease in experienced
hands.
Distant metastases should be assessed by CT scan-
ning of the chest and upper abdomen, to exclude meta-
static disease to the lungs and liver.3 Magnetic
S91
resonance imaging scanning is not suitable for this
due to the relatively slow acquisition process leading
to movement artefact caused by breathing.
Fluoro-deoxy-glucose positron emission tomog-
raphy combined with computed tomography (F-FDG
PET–CT) scanning may be used to give additional
staging information when it is available, particularly
where staging is difficult clinically (e.g. patient with
trismus) or where there is uncertainty on other
imaging and/or equivocal findings that would preclude
radical treatment. Positron emission tomography (PET)
also has a role in the assessment of recurrent tumours
and can detect recurrence at primary sites, neck nodes
and/or distant metastases.
Supported by the results of the UK PET-Neck rando-
mised controlled trial (RCT) study,5 F-FDG PET–CT
scanning is now also recommended for the assessment
of response approximately three months post-chemora-
diotherapy, particularly in patients with advanced
nodal disease. PET-CT guided active surveillance
showed similar survival outcomes to the planned
neck dissection arm, but resulted in considerably
fewer neck dissections, and fewer complications, and
was cost effective, supporting its use in routine
practice.5
Examination under anaesthetic and panendoscopy
Examination under anaesthetic and panendoscopy is
strongly recommended to assess the extent and resect-
ability of the primary tumour and to exclude second
primaries, especially in hypopharynx and oesopha-
gus. Examination under anaesthetic is mandatory if
thorough endoscopic examination is not possible in
the clinic as above and/or if no biopsy can be
obtained.
Recommendations
• Cross-sectional imaging is required in all
cases to complete assessment and staging (R)
• Magnetic resonance imaging is recommended
for primary site and CT scan for neck and
chest (R)
• Positron emission tomography combined with
computed tomography scanning is
recommended for the assessment of response
after chemoradiotherapy, and has a role in
assessing recurrence (R)
• Examination under anaesthetic is strongly
recommended, but not mandatory (R)
Pre-treatment staging
Pre-treatment staging for the primary tumour based
on the tumour–node–metastasis classification (7th
edition) for oropharyngeal tumours is shown in Box I.
S92
BOX I
TNM STAGING FOR OROPHARYNGEAL SQUAMOUS
CELL CARCINOMA
• TX: Primary tumour cannot be assessed
• T0: No evidence of primary tumour
• Tis: Carcinoma in situ
• T1: Tumour 2 cm or less in greatest dimension
• T2: Tumour larger than 2 cm but 4 cm or less in
greatest dimension
• T3: Tumour larger than 4 cm in greatest
dimension or extension to lingual surface of
epiglottis
• T4a: Tumour invades the larynx, deep/extrinsic
muscle of tongue, medial pterygoid, hard palate
or mandible
• T4b: Tumour invades lateral pterygoid muscle,
pterygoid plates, lateral nasopharynx, or skull
base or encases carotid artery
Pathology
Formal tissue biopsy of the primary cancer is one of the
cornerstones of the management pathway in oropharyn-
geal cancer. Tumours can be biopsied under local or no
anaesthetic in the clinic. Otherwise, direct biopsy and
staging under general anaesthetic is necessary.
In very few circumstances, a positive cancer diagno-
sis from fine needle aspiration (FNA) of involved
nodes may suffice, provided the cytology result has
been considered in conjunction with the clinical pres-
entation and appropriate imaging at a head and neck
cancer multidisciplinary team meeting. Such circum-
stances may arise in a person who is unfit to have an
anaesthetic for an open biopsy and in whom local
anaesthetic biopsies have not been successful. There
is limited information on the reliability of p16 and
HPV tests on FNA material and HPV testing is not cur-
rently routinely recommended on FNA samples.
The majority of oropharyngeal cancers are squamous
cell carcinomas. It is recommended that they are
reported according to The Royal College of
Pathologists UK Guidelines for the histopathology
reporting of mucosal malignancies of the pharynx
(2013). Human papilloma virus testing is a core item
for OPSCC to allow the stratification of treatment out-
comes. Human papilloma virus status should be
assessed using validated methods with appropriate con-
trols. Human papilloma virus testing for oropharyngeal
cancer should be performed within a diagnostic service
where the laboratory procedures and reporting standards
are quality assured. The immunohistochemical identifi-
cation of over-expression of p16 protein is a useful
screening method for HPV infection as HPV-associated
carcinomas show strong nuclear and cytoplasmic
expression of p16 in over 70 per cent malignant cells
H MEHANNA, M EVANS, M BEASLEY et al.
and p16-negative cases are almost certainly not HPV
associated. Carcinomas showing p16 over-expression
should have the presence of HPV confirmed by high-
risk HPV DNA in situ hybridisation, if possible.
Polymerase chain reaction analysis for HPV is not cur-
rently recommended in clinical practice as there is a
risk of false positive results from formalin-fixed
tissues.6
Recommendations
• Histological diagnosis is mandatory in most
cases, especially for patients receiving
treatment with curative intent (R)
• Oropharyngeal carcinoma histopathology
reports should be prepared according to The
Royal College of Pathologists Guidelines (G)
• Human papilloma virus testing should be
carried out for all oropharyngeal squamous
cell carcinomas as recommended in The Royal
College of Pathologists Guidelines (R)
• Human papilloma virus testing for
oropharyngeal cancer should be performed
within a diagnostic service where the
laboratory procedures and reporting
standards are quality assured (G)
Prognosis
Prognosis is dependent on stage at presentation as well
as HPV status.7 The status of human papilloma virus is
a strong and independent prognostic factor for survival,
and HPV-positive OPSCC has a 58 per cent reduction
in the risk of death compared with HPV-negative
OPSCC (hazard ratio 0.42, 95 per cent; confidence
interval 0.27–0.66), with 3 year overall survival rates
of 82.4 per cent for HPV-positive disease compared
with 57.1 per cent ( p < 0.001) for HPV-negative
disease.8 Factors including smoking, particularly
current smoking,9,10 which may be a surrogate of
genetic instability, and nodal stage, may influence prog-
nosis in HPV-positive OPSCC. Several immunological
markers have also been shown to correlate with progno-
sis and a UK study showed significant associations
between the presence of tumour infiltrating lympho-
cytes and improved survival.11 Although there are no
head-to-head comparisons of primary surgical vs non-
surgical management for OPSCC, similar survival
outcomes have been reported in studies of primary che-
moradiotherapy and of surgery followed by post-
operative radiotherapy (RT) and/or chemoradiotherapy,
albeit there is a lack of prospective randomised trials of
surgical management.8,12–14
To date, there is no evidence that patients with HPV-
positive and HPV-negative OPSCC should be treated
differently, outside of the context of randomised,
OROPHARYNGEAL CANCER: UK GUIDELINES
controlled clinical trials. In view of the excellent prog-
nosis from lower-risk HPV-positive disease, current
and future UK studies (De-Escalate HPV,
ISRCTN33522080 and PATHOS, UKCRN ID 18645)
will investigate whether reduced intensity treatment
can maintain favourable outcomes but reduce acute
and late toxicity for patients. On the other hand,
because HPV-negative and higher risk HPV-positive
patients have a poorer prognosis, future trials
(CompARE, ISRCTN41478539) will investigate
whether escalating treatment will result in better outcomes
for these patients.
Management
Early (T1–T2 N0) oropharyngeal carcinoma
General principles of management. Early stage (T1–T2
N0 M0) oropharyngeal carcinoma should ideally be
treated with single modality therapy, either primary
surgery or RT. There are no high-quality comparative
studies of the two treatment modalities within the same
population. Retrospective case series demonstrate five-
year disease-specific survival rates of 81–100 per cent
for primary surgery15(with adjuvant therapy where appro-
priate) and 77–89 per cent for primary RT, with surgical
salvage.16 Treatment decisions are made based on the size
and position of the tumour overall functional deficit.
Surgical management of early (T1–T2 N0) oropharyn-
geal cancer. Surgery for T1–T2 N0 OPSCC should
usually be carried out transorally, either by transoral
laser microsurgery (TLM) or transoral robotic surgery
(TORS). Oncologic results after transoral resection of
the oropharynx appear to be comparable to open
surgery and good functional outcomes have been
reported after transoral surgery in retrospective
series.17 Open approaches are associated with increased
severe morbidity and treatment complications and have
now fallen out of favour for early stage disease.
During TLM, tumours are removed in several (at
least two) planned pieces following trans-tumoural
resection. This can cause difficulty in pathological
scrutiny of the resected tissue to determine margins,
which is compounded by laser artefact and difficulty
in orientation. Representative marginal biopsies, taken
from the peripheral mucosal resection margins and
tumour bed can be carried out and examined patho-
logically to help rule out the presence of residual
microscopic disease after TLM. In contrast to TLM,
TORS involves en bloc removal of the tumour in the
majority of cases. As a result, surgical margins can
be more easily interpreted.
About 10–31 per cent of patients who are clinically
T1–T2 N0 will have occult nodal disease. Therefore,
patients having surgery to the primary should also
undergo ipsilateral selective neck dissection. Surgery
to the contralateral neck may also be considered in
tumours arising at or very near the midline (in the
soft palate, tongue base or posterior pharyngeal wall)
S93
in order to obtain pathological staging of the contralat-
eral neck. Evidence suggests dissecting levels II, III
and IV and possibly level I if there is anterior exten-
sion.18 Retrospective studies suggest that level IIb
does not need to be dissected, as long as there are no
findings pre-operatively of level IIa disease. For trans-
oral resections, the neck dissection may be performed
at the same time, or as a staged procedure, around
two weeks before transoral resection of the primary.
A staged approach may help prevent the development
of a fistula if there is lateral pharyngeal wall transoral
resection. Concomitant transoral resection and neck
dissection can also be carried out and good results
have been reported. In the latter, local muscle transpos-
ition (digastric or sternomastoid) can be performed to
augment any defect and decrease risk of fistula. For
any transoral resection of the oropharynx, ligation of
the individual feeding vessels from the external
carotid artery should be performed (ascending pharyn-
geal, lingual and facial branches) to limit the risk of
potentially life-threatening haemorrhage. This should
be done in any neck dissection performed as a prior
staged procedure.
Although the goal for T1–T2 N0 disease should be
single modality treatment, adjuvant RT and/or chem-
oradiotherapy may be required due to adverse patho-
logical features for recurrence following surgery.
Post-operative RT should be planned using the same
principles as radical RT; a dose of 60 Gy in 30 fractions
is typically recommended. Adjuvant treatment may
affect functional outcomes following surgery.
Radical RT for early oropharyngeal cancer. Prior to RT,
patients should undergo dietetic, speech and language
therapy and dental review. A total dose equivalent of
70 Gy in 35 fractions is used in radical treatment.
Hypofractionated schedules (typically 65–66 Gy in 30
fractions) are frequently used. Patients are managed as
category 1 patients and RT should be completed on time.
Target volume definition is performed using a con-
trast-enhanced planning CT scan. Co-registration of
the planning CT scan with the diagnostic MRI scan
can aid target volume delineation. An anatomical
(inclusion of the whole oropharynx) or geometric
(inclusion of gross tumour volume with a defined
margin) approach may be used for primary target
volume delineation. Prophylactic RT should be given
to the ipsilateral cervical lymph nodes for lateralised
(e.g. tonsillar) tumours and to both sides of the neck
for non-lateralised tumours (defined as tumours
which involve greater than 1 cm of a midline structure
e.g. soft palate and/or tongue base). Radiotherapy to
levels II, III and IVa is recommended; level Ib may
also be included in cases with anterior extension of
tumour and/or involvement of the anterior tonsillar
pillar. Planning can be carried out using three-dimen-
sional conformal planning (typically using a ‘wedged
pair’ of RT fields) or intensity modulated radiotherapy
(IMRT) and/or Arc therapy.
S94
Recommendations
• Treatment options for T1–T2 N0
oropharyngeal squamous cell cancer include:
radical radiotherapy or transoral surgery and
neck dissection (with post-operative
(chemo)radiotherapy if there are adverse
pathological features on histological
examination) (R)
• Transoral surgery is preferable to open
techniques and is associated with good
functional outcomes in retrospective series (R)
• If treated surgically, neck dissection should
include levels II–IV and possibly level I. Level
IIb can be omitted if there is no disease in level
IIa (R)
• If treated with RT, levels II–IV should be
included, and possibly level Ib in selected
cases (R)
Advanced (T3–T4 N0 and T1–T4 N1–N3)
oropharyngeal cancer
General principles of management. A thorough review
of the literature relating to the management of oropha-
ryngeal cancer was published as a Cochrane report in
2009. The only evidence of statistically significant
benefit was for the addition of concomitant chemother-
apy to post-operative RT.19 All other treatment compar-
isons did not show any statistical differences.
In recent years, there has been a tendency to offer
primary RT and/or chemoradiotherapy for oropharyn-
geal carcinoma, as part of an ‘organ preservation’
strategy. Although there are no good head-to-head com-
parisons of primary surgery and chemoradiotherapy for
stage III/IV OPSCC, outcomes from randomised trials
of chemoradiotherapy (e.g. RTOG 0129) are at least
comparable to the results of surgical series. One poten-
tial concern with an organ preservation approach is
that although salvage surgery has been shown to have
a high success rate for laryngeal cancer, the success
rate of salvage surgery is not the same in other head
and neck sites, such as the oropharynx.
The 2013 National Head and Neck Cancer Audit (9th
DAHNO Report) concluded that variation in treatment
strategies for OPSCC is evident across cancer networks
in England and Wales. This is not surprising in view of
the fact that current published evidence does not provide
a consensus view to define the most appropriate treat-
ment strategy. Treatment decisions for individual
patients will depend on the size, position and overall
functional deficit, as well as on patient preference and
local expertise. Human papilloma virus status has a pro-
found influence on prognosis, and in future, could
potentially affect selection of treatment modality.
Recruitment into randomised controlled clinical trials
addressing these issues is highly recommended.
H MEHANNA, M EVANS, M BEASLEY et al.
Surgical management of advanced oropharyngeal car-
cinoma. Where facilities and expertise exist, transoral
resection (by TLM or TORS) of base of tongue, tonsil
and pharyngeal wall primary tumours (usually with
post-operative (chemo)radiotherapy) has been shown
to offer rates of cure which appear to be as good as
primary chemoradiotherapy in non-randomised compar-
isons, with promising functional results. Transoral resec-
tion is generally restricted to T1–T2 tumours, although
resection of some T3 tumours may be considered if it
is anticipated that negative margins can be achieved
via a transoral approach. Transoral resection is rarely
appropriate for T4 primary tumours. Also, where a
larger resection of the soft palate is required, the
general consensus is that surgery gives a poor functional
outcome. It should be noted that approximately 80 per
cent of patients who undergo primary surgery will
also receive post-operative RT or chemoradiotherapy.
If transoral resection is not appropriate, e.g. for large
primary tumours, then chemoradiotherapy should be
considered. Alternatively, open surgical procedures
may be considered, which usually require paramedian
mandibulotomy for access and reconstruction with a
flap. Trans-cervical pharyngotomy alone can be used
for tongue base resections. Other approaches, such as
glossotomy and lingual release can be used but are not
often employed. Reconstruction is generally performed
using radial artery free flaps or anterolateral thigh free
flaps. Reconstruction using pedicled flaps, such as pec-
toralis major should be considered sub-optimal.
Functional results following open surgery can be poor,
particularly when followed by adjuvant therapy.
There are several published case series that report the
likelihood of nodal metastasis for advanced oropharyn-
geal carcinoma to be over 50 per cent. When managing
T3 and T4 oropharyngeal cancers, the N0 neck should
be treated electively. When managing the N0 neck sur-
gically, a selective level II, III and IV neck dissection is
generally recommended, and in some cases level I may
be included. All patients with node positive disease
should have a modified neck dissection or at least
level I–IV selective neck dissection.
Primary chemoradiotherapy for loco-regionally advanced
(stage III–IVb) oropharyngeal carcinoma. Chemoradio-
therapy (organ preservation) is an effective treatment
choice for advanced head and neck tumours. A RT
dose equivalent of 70 Gy in 2 Gy fractions with con-
current cisplatin chemotherapy is considered standard
for stage III and/or IV OPSCC. Concurrent weekly
cetuximab (a monoclocal antibody targeting the epider-
mal growth factor receptor) may be given with RT if
there is a contraindication to platinum chemotherapy
(e.g. renal dysfunction or hearing impairment).
Alternatively, radical RT alone can be given for patients
with advanced disease who are not fit for concurrent
treatment, particularly if they are over 70 years of age
when the benefits of concurrent chemotherapy are
reduced. Induction chemotherapy may be considered
OROPHARYNGEAL CANCER: UK GUIDELINES
for patients with advanced (T4, N3, N2c) disease to
reduce the risk of distant metastases20 and for selected
other patients with bulky primary (T4) and/or nodal
disease (N3), but there is currently no high-quality evi-
dence of its efficacy in these indications.
The principles of RT outlining and planning are as
described for earlier stage disease. Neck nodes should
be included in the treatment fields depending on their
probability of involvement and according to the
DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI,
RTOG, TROG consensus guidelines and atlas which
were updated in 2013.21 Radiotherapy to levels Ib–IVa,
V(a,b) and the retropharyngeal nodes (level VIIa) at the
level of the oropharynx is generally recommended in a
node positive neck. The retrostyloid space (level VIIb)
is included when level II is involved and the supraclavicu-
lar fossa (levels IVb and Vc) is included when level IVa
or V is involved. Radiotherapy should be given to at least
the ipsilateral cervical lymph nodes for lateralised
tumours and to both sides of the neck for non-lateralised
tumours. The issue of whether the contralateral neck
should be treated in patients with lateralised oropharyn-
geal tumours and advanced (N2+) nodal disease
remains controversial and will depend on local practice.
Chemoradiotherapy is associated with greater toxicity
than RT alone and late toxicity, particularly swallowing
dysfunction, can have a significant impact on quality of
life.22 Gastrostomy tube dependence rates of up to 24 per
cent at 1 year and 14 per cent at 2 years post-chemora-
diotherapy have been reported, although others have
reported much lower rates. Improvements in RT techni-
ques (including IMRT) have been shown to reduce late
complications following RT. The UK PARSPORT ran-
domised study showed a significant reduction in xeros-
tomia rates with parotid sparing IMRT compared with
conventional RT (using parallel opposed fields) in
patients with advanced OPSCC.23 Ongoing studies are
exploring the role of IMRT in improving swallowing
function following RT, by reducing radiation dose deliv-
ery to the pharyngeal constrictor muscles and other
swallowing structures.
Traditionally, patients with advanced nodal disease
(N2 or N3) being treated by chemoradiotherapy
required a planned neck dissection, with little evidence
to support whether neck dissection before or after che-
moradiotherapy is more effective. There is now level I
evidence from the PET-Neck trial that a PET–CT
guided active surveillance policy, with neck dissection
only being carried out if residual abnormal or equivocal
nodes are present on imaging 10–12 weeks after the
end of chemoradiotherapy, results in similar survival
rates to a planned neck dissection, with less morbidity,
and with higher cost effectiveness.5
Post-operative radiotherapy and chemoradiotherapy for
advanced oropharyngeal carcinoma. The indications
for post-operative RT and chemoradiotherapy for
OPSCC depend on pathological risk factors for recur-
rence common to most head and neck squamous
S95
carcinomas. Randomised controlled trials and a meta-
analysis of results confirm that patients with extra-cap-
sular invasion and/or microscopically involved
(<1 mm) surgical resection margins around the
primary tumour experience significant benefit in
terms of overall and disease free survival from post-
operative chemoradiotherapy compared with RT
alone.24 Post-operative chemoradiotherapy is asso-
ciated with significant acute and late toxicity and is
not generally recommended in patients over 70 years
of age and/or patients with poor performance status.
Indications for post-operative RT alone include mul-
tiple nodal metastasis, T3 or T4 tumours, and
tumours with other adverse features, including peri-
neural or lymphovascular invasion. Patients with
close (1–5 mm) surgical margins around the primary
tumour may be treated with post-operative chemora-
diotherapy or RT alone according to the presence or
absence of other risk factors for recurrence. Patients
should start their adjuvant RT as soon as possible
after surgery (ideally within five weeks (35 days) and
no later than six weeks (42 days)) to avoid reduced
local control and survival due to protracted treatment.
The relevance of traditional risk factors for recurrence
(including extra-capsular spread) and the benefit of
adjuvant chemotherapy with RT in the context of
HPV-positive OPSCC has been questioned by some
studies. However, no change in management of patients
should occur outside clinical trials. Clinical trials which
aim to modify adjuvant treatment based on HPV status
are currently ongoing in the UK and USA.
Ongoing Research
Human papilloma virus status appears to have profound
influence on prognosis and, in the future, potentially on
selection of treatment modality. There are several
ongoing or planned clinical trials for HPV-positive
and HPV-negative OPSCC and recruitment into clinical
trials addressing these issues is highly recommended.
Development of biomarker classifiers for treatment
selection is also high recommended.
Recommendations
• Advanced oropharyngeal carcinoma can be
treated with primary chemoradiotherapy or
transoral surgery and adjuvant
(chemo)radiotherapy (R)
• The N0 neck should be treated electively –
either by radiotherapy or selective neck
dissection (R)
• Patients with advanced nodal (N2 or N3)
disease receiving radical chemoradiotherapy
should have a PET-CT scan 10–12 weeks
after treatment, with a subsequent neck
dissection within 4 weeks if residual abnormal
or equivocal nodal disease is detected (R)
S96
• Intensity modulated radiotherapy reduces
toxicity in patients treated with radical
radiotherapy, compared with conventional
radiotherapy (R)
• Post-operative chemoradiotherapy is
currently recommended in patients treated
with surgery who have involved primary
tumour resection margins and/or
extracapsular spread of nodal disease.
Otherwise, post-operative radiotherapy alone
may be indicated (R)
Key points
• Oropharyngeal cancer incidence is increasing rapidly
in the UK due to the Human papillomavirus (HPV).
• HPV association confers better outcomes regardless
of treatment modality
• Early stage disease should be receive single modality
treatment
• Advanced disease should receive combined modal-
ity treatment
• PETCT scanning undertaken at 10-12 weeks post
chemo-radiation results in similar survival to
planned neck dissection, but with considerably
fewer patients requiring neck dissection, less mor-
bidity and is cost-effective
• There is insufficient evidence to alter treatment on
the basis of HPV status
• Patients should be offered the opportunity to partici-
pate in the ongoing clinical trials.
References
1 Nasman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G,
Ahrlund-Richter S et al. Incidence of human papillomavirus
(HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epi-
demic of viral-induced carcinoma? Int J Cancer 2009;125:362–66
2 Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C,
Paleri V et al. Prevalence of human papillomavirus in oropha-
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J Laryngol Otol 2016;130(Suppl S2):S28–31
4 Olliff J, Richards P, Connor S, Wong WL, Beale T, Madani G.
Head and neck cancers. In: Nicholson T, ed. Recommendations
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Pawlita M et al. A novel algorithm for reliable detection of
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Tan PF et al. Human papillomavirus and survival of patients
with oropharyngeal cancer. N Engl J Med 2010;363:24–35
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geal cancer. J Clin Oncol 2012;30:2102–111
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Suchak K et al. Tumour-infiltrating lymphocytes predict for
outcome in HPV-positive oropharyngeal cancer. Br J Cancer
2014;110:489–500
12 Licitra L, Perrone F, Bossi P, Suardi S, Mariani L, Artusi R et al.
High-risk human papillomavirus affects prognosis in patients
with surgically treated oropharyngeal squamous cell carcinoma.
J Clin Oncol 2006;24:5630–36
13 Haughey BH, Hinni ML, Salassa JR, Hayden RE, Grant DG,
Rich JT et al. Transoral laser microsurgery as primary treatment
for advanced-stage oropharyngeal cancer: a United States multi-
center study. Head Neck 2011;33:1683–94
14 Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H et al.
Improved survival of patients with human papillomavirus-posi-
tive head and neck squamous cell carcinoma in a prospective
clinical trial. J Natl Cancer Inst 2008;100:261–69
15 Cosmidis A, Rame JP, Dassonville O, Temam S, Massip F,
Poissonnet G et al. T1-T2 NO oropharyngeal cancers treated
with surgery alone. A GETTEC study. Eur Arch
Otorhinolaryngol 2004;261:276–81
16 Mendenhall WM, Morris CG, Amdur RJ, Hinerman RW,
Malyapa RS, Werning JW et al. Definitive radiotherapy for tonsil-
lar squamous cell carcinoma. Am J Clin Oncol 2006;29:290–97
17 Moore EJ, Hinni ML. Critical review: transoral laser microsur-
gery and robotic-assisted surgery for oropharynx cancer includ-
ing human papillomavirus-related cancer. Int J Radiat Oncol
Biol Phys 2013;85:1163–67
18 Lim YC, Koo BS, Lee JS, Lim JY, Choi EC. Distributions of
cervical lymph node metastases in oropharyngeal carcinoma:
therapeutic implications for the N0 neck. Laryngoscope 2006;
116:1148–52
19 Furness S, Glenny AM, Worthington HV, Pavitt S, Oliver R,
Clarkson JE et al. Interventions for the treatment of oral cavity
and oropharyngeal cancer: chemotherapy. Cochrane Datab
Syst Rev 2011:CD006386
20 O’Sullivan B, Huang SH, Siu LL, Waldron J, Zhao H, Perez-
Ordonez B et al. Deintensification candidate subgroups in
human papillomavirus-related oropharyngeal cancer according to
minimal risk of distant metastasis. J Clin Oncol 2013;31:543–50
21 Gregoire V, Ang K, Budach W, Grau C, Hamoir M, Langendijk
J et al. Delineation of the neck node levels for head and neck
tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG,
NCIC CTG, NCRI, RTOG, TROG consensus guidelines.
Radiother Oncol 2014;110:172–181
22 Machtay M, Moughan J, Trotti A, Garden AS, Weber RS,
Cooper JS et al. Factors associated with severe late toxicity
after concurrent chemoradiation for locally advanced head and
neck cancer: an RTOG analysis. J Clin Oncol 2008;26:3582–89
23 Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA,
Clark C et al. Parotid-sparing intensity modulated versus con-
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Oncol 2011;12:127–36
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Forastiere A et al. Defining risk levels in locally advanced head
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Address for correspondence:
Prof Hisham Mehanna,
Director, Institute of Head and Neck Studies and Education,
College of Medical and Dental Sciences,
University of Birmingham,
Edgbaston,
Birmingham,
UK
E-mail: H.mehanna@bham.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S97–S103. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000517

Nasopharyngeal carcinoma: United Kingdom

National Multidisciplinary Guidelines

R SIMO1, M ROBINSON2, M LEI3, A SIBTAIN4, S HICKEY5

1
Department of Otolaryngology – Head and Neck Surgery, Guy’s and St Thomas’ Hospital NHS Foundation Trust,
Guy’s, King’s and St Thomas’ Medical and Dental School, London, 2School of Dental Sciences, Newcastle
University, Newcastle-upon-Tyne, 3Department of Oncology, Guy’s and St Thomas’ Hospital NHS Foundation
Trust, London, 4Department of Clinical Oncology, St Bartholomew’s Hospital, London, and 5Department of
Otolaryngology-Head and Neck Surgery, Torbay Hospital, Torquay, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. Although much commoner in the eastern hemisphere, with an age-standardised incidence
rate of 0.39 per 100 000 population, cancers of the nasopharynx form one of the rarer subsites in the head and
neck.1 This paper provides recommendations on the work up and management of nasopharyngeal cancer based
on the existing evidence base for this condition.

Recommendations
• Patients with nasopharyngeal carcinoma (NPC) should be assessed with rigid and fibre-optic nasendoscopy. (R)
• Nasopharyngeal biopsies should be preferably carried out endoscopically. (R)
• Multislice computed tomographic (CT) scan of head, neck and chest should be carried out in all patients and
magnetic resonance imaging (MRI) where appropriate to optimise staging. (R)
• Radiotherapy (RT) is the mainstay for the radical treatment for NPC. (R)
• Concurrent chemoradiotherapy offers significant improvement in overall survival in stage III and IV
diseases. (R)
• Surgery should only be used to obtain tissue for diagnosis and to deal with otitis media with effusion. (R)
• Radiation therapy is the treatment of choice for stage I and II disease. (R)
• Intensity modulated radiation therapy techniques should be employed. (R)
• Concurrent chemotherapy with radiation therapy is the treatment of choice for stage III and IV disease. (R)
• Patients with NPC should be followed-up and assessed with rigid and/or fibre-optic nasendoscopy. (G)
• Positron emission tomography–computed tomography (PET–CT), CT or MRI scan should be carried out at
three months from completion of treatment to assess response. (R)
• Multislice CT scan of head, neck and chest should be carried out in all patients and MRI scan whenever
possible and specially in advanced cases with suspected recurrence. (R)
• Surgery in form of nasopharyngectomy should be considered as a first line treatment of residual or recurrent
disease at the primary site. (R)
• Neck dissection remains the treatment of choice for residual or metastatic neck disease whenever possible. (R)
• Re-irradiation should be considered as a second line of treatment in recurrent disease. (R)

Introduction 20 and 30 per 100 000 inhabitants a year, but in

Nasopharyngeal carcinoma (NPC) is a squamous cell
carcinoma (SCC) arising from the mucosal surface of
the nasopharynx. The most common site is the fossa
of Rosenmüller which is a recess just medial to the
medial crura of the eustachian tube. Nasopharyngeal
carcinoma is frequent in patients of Southern
Chinese, Northern African and Alaskan origin. The
incidence in the Hong Kong population is between
Western countries the adjusted incidence is very low;
around 1 per 100 000 per annum.2
Aetiology and risk factors
The Epstein–Barr virus (EBV) and consumption of
salted fish containing dimethylnitrosamine have been
implicated in its aetiology. Genetic alterations include
S98
deletion of chromosomal regions at 1p, 14q, 16p and
amplification of 4q and 12q.
Clinical presentation
Nasopharyngeal carcinoma is more common in men
than in women (3:1), with a median age at presentation
of 50 years. The most common symptoms are:
• Nasal obstruction
• Epistaxis
• Conductive hearing loss secondary to otitis media
with effusion (OME) due to eustachian tube
orifice obstruction
• Cranial nerve neuropathies secondary to skull base
invasion (cranial nerves III, IV, V and VI)
• Neck lumps and swellings due to cervical lymph
node metastasis, which is usually in the upper
levels of the neck and often bilateral due to the
midline lymphatic drainage of the tumour.
Assessment and staging
Clinical assessment
Full history and otorhinolaryngological examination
with rigid or fibre-optic nasendoscopy in the out-
patient setting should be performed. Examination
under anaesthetic with endoscopic assessment and
biopsy of the nasopharyngeal abnormality is manda-
tory with targeted biopsies of the fossa of
Rosenmüller, when indicated. Biopsies should be
preferably done after staging scans to avoid false
artefacts.
Pathologic considerations
Histological examination is required for the definitive
diagnosis. Fine needle aspiration cytology (FNAC)
can be used as an adjunct for staging neck disease
and distant metastases.
Nasopharyngeal carcinoma (NPC) comprises three
histological types: non-keratinising carcinoma (incorp-
orating differentiated and undifferentiated subtypes),
keratinising carcinoma and basaloid SCC. All NPCs
share morphological and immunohistochemical fea-
tures of squamous differentiation to varying degrees.
Non-keratinising carcinoma is by far the most
common type in both high and low incidence areas.
The diagnosis of keratinising carcinoma and basaloid
SCC is facilitated by the identification of malignant
epithelium that shows overt keratinisation. By contrast,
non-keratinising carcinoma has subtle morphological
features that are often obscured by a dense lymphoid
stroma, from which the synonym lymphoepithelial car-
cinoma is derived. Immunohistochemistry is required
to identify the production of keratin intermediate fila-
ments. Antibodies AE1/AE3 and MNF116 can be
used to detect of a broad range of keratin molecules
R SIMO, M ROBINSON, M LEI et al.
and when the malignant cells are positive they
support a diagnosis of carcinoma. Cytoplasmic expres-
sion of cytokeratins 5/6 and nuclear expression of p63
can be used as evidence of squamous differentiation.
Epstein–Barr virus (EBV) has been recognised as a
primary aetiological agent in non-keratinising NPC.
The presence of EBV is most reliably detected using
in situ hybridisation for EBV encoded early RNA
(EBER), whereas the expression of latent membrane
protein-1 is less sensitive and is positive in about a
third of cases.
Serological markers of EBV infection are detected
in almost all cases of non-keratinising carcinoma,
but have limited diagnostic utility. They can be used
as an adjunct to monitor disease progression and
response to treatment, although the practical clinical
use remains unproven. Detection of immunoglobulins
to viral capsid antigen and early antigens are the most
commonly used tests. In addition, the detection of
EBV nucleic acid (DNA and RNA) in serum and
plasma, using quantitative polymerase chain reaction
techniques, has been developed to aid disease
surveillance.
Human papilloma virus (HPV) has been recognised
as a primary aetiological agent in a subset of head and
neck SCCs, primarily oropharyngeal in origin. A
number of studies have reported HPV-positivity in
NPCs, either with or without concurrent EBV associ-
ation. The clinical significance of this relationship
has not yet been established.
Imaging considerations
Staging investigations should include multislice com-
puted tomography (CT) scan of the head, neck and
chest. Magnetic resonance imaging (MRI) scans of
the skull base are useful especially in locally advanced
tumours. The use of positron emission tomography–
computed tomography (PET–CT) should be reserved
for patients with a suspected occult primary tumour
in the nasopharynx and should be carried out before
diagnostic procedure. Ultrasound guided FNAC of
suspected cervical lymph node metastases is recom-
mended, if they cannot be definitively labelled as
malignant on cross-sectional imaging.
Staging
See Tables I–IV.
TABLE I
PRIMARY TUMOUR (T)
T1 Tumour confined to nasopharynx or extends to
oropharynx and/or nasal cavity
T2 Tumour with parapharyngeal extension
T3 Tumour invades bony structures and/or paranasal sinuses
T4 Tumour with intracranial extension and/or involvement
of cranial nerves, infratemporal fossa, hypopharynx, orbit
or masticator space
NASOPHARYNGEAL CARCINOMA: UK GUIDELINES S99

TABLE II surgical treatment unacceptably morbid as a first line

REGIONAL LYMPH NODE METASTASES (N) option. The therapeutic ratio of RT is improved by
the addition of synchronous chemotherapy (CT) and
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis advances in radiation delivery techniques, both of
N1 Unilateral metastasis in lymph nodes, 6 cm or less in the which may help to achieve improved disease control
greatest dimension, above the supraclavicular fossa and survival along with lower rates of long-term
N2 Bilateral metastasis in lymph nodes, 6 cm or less in the toxicity. Intensity modulated radiotherapy (IMRT)
greatest dimension, above the supraclavicular fossa.
N3 Metastasis in a lymph node greater than 6 cm in delivery techniques allow concavities to be created in
dimension or extension to the supraclavicular fossa the RT dose distribution, which is particularly useful
N3a for the treatment of head and neck cancer. It facilitates
Greater than 6 cm in dimension
N3b improved dosimetric coverage of the primary tumour
Extension to the supraclavicular fossa volume, particularly in the pharyngeal recesses, and
sparing of normal organs, including the parotid
gland, substantially reducing long-term xerostomia,
TABLE III thereby improving quality of life.
DISTANT METASTASIS (M) Proton beam therapy is a newly emerging technology
which may further improve radiation dose conformality.
Mx Distant metastasis cannot be assessed
M0 No distant metastasis Evidence to support a difference in outcomes compared
M1 Distant metastasis to those achieved with conventional radiotherapy is
lacking. Currently, nasopharyngeal tumours in paediatric,
teenage and young adult patients, are included as permit-
ted indications in the NHS England Proton Programme
TABLE IV and these patients should be referred accordingly.
STAGE GROUPING Radiotherapy is also useful in the palliative setting. It
can be used to treat symptomatic metastases and local
Stage 0 Tis N0 M0
Stage I T1 N0 M0 disease in the presence of widespread metastases when
Stage II T2 N0 M0 aggressive local therapy is clinically inappropriate.
T1 N1 M0
T2 N1 M0
Stage III T1 N2 M0 Recommendation
T2 N2 M0
T3 N0 M0
T3 N1 M0 • Radiotherapy is the mainstay for the radical
T3 N2 M0 treatment for NPC (R)
Stage IVa T4 N0 M0
T4 N1 M0
T4 N2 M0 Chemotherapy
Stage IVb Any T N3 M0
Stage IVc Any T Any N M1 There is evidence confirming significant improvement
in overall survival (OS) in the patients treated concur-
rently with chemoradiotherapy for NPC as compared
to RT alone. The addition of chemotherapy has been
shown to confer a small, but significant benefit in OS
Recommendations and event-free survival (EFS). A meta-analysis of
eight randomised trials and 1753 patients reported an
• Patients with NPC should be assessed with 18 per cent reduction in the hazard ratio for death
rigid and fibre-optic nasendoscopy (R) with the use of any form of chemotherapy with RT, cor-
• Nasopharyngeal biopsies should preferably responding with an absolute survival benefit of 6 per
be carried out endoscopically (R) cent at five years. The greatest benefit was observed
• Multislice CT scan of head, neck and chest with concomitant chemotherapy. The roles of neo-
should be carried out in all patients and MRI adjuvant and adjuvant chemotherapy are more contro-
where appropriate to optimise staging (R) versial with no proven survival advantage but
confirmed EFS benefit with neo-adjuvant chemother-
apy. Adjuvant chemotherapy after RT is less well toler-
ated and benefits are still unproven. Cisplatin-based
Management chemotherapy is used concurrently with radiation and
combination of cisplatin and fluorouracil may be used
Radiotherapy in the neo-adjuvant setting, in selected cases.
Radiotherapy (RT) is the mainstay for the radical treat- Platinum-based chemotherapy has been effective in
ment for nasopharyngeal carcinoma (NPC).3 The ana- palliation of recurrent and metastatic NPC. Single
tomical location, propensity for loco-regional spread, centre (level 2) studies have reported activity with the
and proximity of critical structures makes wide field use of capecitabine, gemcitabine and taxanes as
S100
single agent or in combination with platinum for
second- and third-line treatments for metastatic disease.
A randomised trial including 803 patients with stages
III–IVB NPC compared induction and concurrent
chemotherapy, replacement of fluorouracil with oral
capecitabine and/or accelerated RT found no benefit by
changing to an induction–concurrent sequence.4–7
Recommendation
• Concurrent chemoradiotherapy offers
significant improvement in OS in stage III and
IV diseases (R)
Primary surgery
Surgery is only used in the following scenarios:
• To obtain tissue for diagnosis. Contact endoscopic
diagnosis of NPC remains experimental
• To obtain tissue from clinically involved neck
nodes using FNAC or core biopsy. If these techni-
ques are non-diagnostic, open biopsy can be used.
In cases with obvious fungation open biopsy is the
method of choice
• To deal with OME.
Recommendation
• Surgery should only be used to obtain tissue
for diagnosis and to deal with otitis media
with effusion (R)
Treatment recommendations
Stages I and II
Patients with early disease can be treated with RT alone,
resulting in disease free survival rates of 90 and 84 per
cent. The dose to the primary tumour should be equivalent
to 70 Gy in 2 Gy fractions and at least 50 Gy in 2 Gy
fractions to the bilateral neck and other sites of potential
microscopic spread. Intensity modulated radiotherapy
techniques should be used. Evidence of benefit from the
addition of chemotherapy to RT in early disease is lacking.
Intermediate stage II disease can be treated with RT
alone (T2N0M0), but most cases are treated with combin-
ation chemoradiotherapy. Intensity modulated radiother-
apy should be considered mandatory. A dose of 70 Gy is
recommended to the primary, 66–70 Gy to gross disease
in lymph nodes and 50 Gy to the bilateral neck and other
sites of potential microscopic spread. Radiobiological
equivalents are given if a fraction size other than 2 Gy
is employed, for example with intensity modulation.
The most commonly used chemotherapy schedule is cis-
platin 100 mg/m2 on days 1, 22 and 43 of RT based on
the United States Intergroup Study 0099. Weekly
R SIMO, M ROBINSON, M LEI et al.
cisplatin at a dose of 40 mg/m2 is effective, but has not
been compared with the standard regimen in a rando-
mised study. It can be considered for older patients
and/or those with significant comorbidities.
Stages III and IV
Concurrent chemoradiotherapy is the standard of care
for advanced nasopharyngeal cancers. This improves
OS by up to 6 per cent at five years compared with
radical RT. A dose of 70 Gy (2 Gy per fraction) with
concurrent cisplatin chemotherapy is recommended.
Several trials have explored the role of neo-adjuvant
chemotherapy, with a recent meta-analysis confirming
an improvement in disease-free survival, whilst
having no effect on OS. Radiotherapy target volume
definition must include gross tumour (clinical, endo-
scopic and radiological), the nasopharynx and the pter-
ygopalatine fossa, the base of skull and clivus, the
posterior part of sphenoid sinus, the posterior third of
the nasal cavity and the maxillary sinus, retropharyn-
geal lymph nodes and parapharyngeal space.
Prophylactic irradiation must include uninvolved level
I–V nodal areas.
IMRT is used with either fixed gantry linear acceler-
ator-based techniques (fixed field or volumetric arc) or
with helical tomotherapy techniques with confirmed
benefits in preserving parotid gland function. Studies
are currently exploring the role of further dose escal-
ation with IMRT to improve local control.8–10
Surgical treatment is reserved for salvage following
chemoradiotherapy failure.
Recommendations
• Radiation therapy is the treatment of choice
for stage I and II diseases (R)
• Intensity modulated radiation therapy
techniques should be employed (R)
• Concurrent chemotherapy with radiation
therapy is the treatment of choice for stage III
and IV diseases (R)
Assessment of treatment response and
follow-up
Assessment of treatment response and follow-up is
imperative in nasopharyngeal carcinoma (NPC).
Patients should be assessed clinically with endoscopic
examination and neck palpation. Currently there is no
consensus on the best mode of radiological assessment
to determine completeness of response to treatment.
PET–CT, CT or MRI follow-up scans have been
adopted in some centres at three months and at a year
from completion of treatment.
Following treatment, it can take up to three months
for NPC to disappear histologically. Post-treatment
disease can be monitored using biopsies. However,
accurate interpretation of the material can be
NASOPHARYNGEAL CARCINOMA: UK GUIDELINES
confounded by persistent areas of degenerate tumour,
the biological significance of which needs to be
assessed in the context of the temporal relationship to
treatment. Furthermore, tissue changes in the radiation
field can also mimic residual disease and need to be
interpreted with caution. The presence of morphologic-
ally viable malignant cells with evidence of EBER by
in situ hybridisation is strongly suggestive of residual
disease. If a biopsy contains carcinoma, repeat sam-
pling two weeks apart is recommended and remission
is defined as two sequential negative biopsies. The
recommended follow-up strategy is addressed else-
where in the guidelines.
Recommendations
• Patients with NPC should be followed-up and
assessed with rigid and/or fibre-optic
nasendoscopy (G)
• Positron emission tomography–computed
tomography, CT or MRI scan should be
carried out at three months from completion
of treatment to assess response (R)
• Multislice CT scan of head, neck and chest
should be carried out in all patients and MRI
scan whenever possible and specially in
advanced cases with suspected recurrence (R)
Management of residual and recurrent
disease
Surgery
Chemoradiotherapy or RT resistant tumours may be
amenable to salvage surgery to the primary site or the
neck. Surgery for recurrence is associated with less
morbidity than re-irradiation of recurrent disease.
Nasopharyngectomy and/or neck dissection should
be the first option for locoregional residual and recur-
rent disease. When surgery is not possible either pallia-
tive chemotherapy or re-irradiation should be considered.
Surgery to the primary site. Endoscopically guided
microwave coagulation of small volume (rT1) recurrent
disease has been described as having low morbidity
with OS and local progression-free survival of 93.6
and 90.7 per cent at five years.
The likelihood of successful surgical excision
diminishes in proportion to the size and extent of the
recurrent and/or persistent disease at the primary site.
Transcranial approaches are associated with high mor-
bidity. Transnasal and transantral approaches provide
poor access to the paranasopharyngeal space.
Experience with combined transoral and transnasal
endoscopic resection is increasing and may become
the favoured approach for small lesions, because of
the low associated morbidity. Robotic surgical
S101
techniques, although used in only a few studies, have
been shown to offer equivalent local control in highly
selected cases.
The anterolateral approach with maxillary swing
(facial translocation) allows access to the nasopharynx
and paranasopharyngeal space and has a local control
rate of up to 62 per cent. Palatal fistulae occur in
20–25 per cent of patients, whilst 60 per cent have
some degree of trismus. A lateral approach with
radical mastoidectomy and exposure of the infratem-
poral fossa after mobilisation of the internal carotid, tri-
geminal nerve and floor of the middle cranial fossa has
been described. Its use is associated with considerable
risk of morbidity.11–13
Surgery to the neck. Re-irradiation of the involved neck
to treat persistent and/or recurrent disease carries a
high risk of tissue necrosis and fibrosis. Persistent or
recurrent nodal disease following chemoradiotherapy
demonstrates a high incidence of extracapsular exten-
sion (54–65 per cent). For this reason salvage radical
neck dissection (with the placement of brachytherapy
tubes for after loading where there is extensive
disease), remains the treatment of choice. It may be
necessary to excise involved skin and repair with
pedicled or microvascular flaps. Transferred tissue
flaps should be placed so as to overlie brachytherapy
tubes as they are often more tolerant of irradiation
than previously irradiated skin. Salvage neck dissection
gives up to 66 per cent five-year local control of
disease.14
Non-surgical options
Re-irradiation. Local nasopharyngeal recurrences
respond better to re-irradiation than other sites.15 The
scope for re-irradiation depends on the tumour
volume, current T stage and the disease free interval
or time since primary irradiation. The dose that can
be delivered depends on the dose received by adjacent
critical organs, time since initial irradiation and the
technique of RT delivery. In general, a dose of
greater than 50 Gy needs to be deliverable for re-irradi-
ation to be worthwhile. This is more achievable using
highly conformal techniques, including IMRT, intraca-
vitary and interstitial brachytherapy, stereotactic radio-
surgery, fractionated stereotactic RT or proton beam
therapy. Overall survival rates of 60 per cent at five
years have been reported. The toxicity rate for re-irradi-
ation is significant. A prognostic scoring system for
locally recurrent nasopharyngeal carcinoma (NPC)
has been validated. When re-irradiation is not possible,
then palliative chemotherapy should be considered.
Conventional chemotherapy. Palliative systemic chemo-
therapy is the central component of the treatment for
metastatic disease.16 Cisplatin-based chemotherapy
produces response rates of up to 80 per cent in chemo-
therapy-naive patients resulting in median survival
rates of up to 15 months. There are no randomised
S102
comparisons of different chemotherapy schedules.
Whilst cisplatin and fluorouracil remain the most
widely used combinations, the gemcitabine and cis-
platin doublet has also been shown to produce high
response rates and be well tolerated, and can be consid-
ered above other agents that have higher toxicity.
Triplet combinations also produce higher response
rates, but at the cost of higher toxicity. The decision
to give palliative chemotherapy should take into
account previous therapy and the performance status
of the patient.
Molecular therapies and immunotherapy
There is no evidence for the routine use of molecular
therapies for metastatic NPC outside clinical trial set-
tings. Phase II trials have demonstrated limited activity
in the second- and third-line settings. The utility of
immunotherapy based either adoptive or active means
against Epstein–Barr virus (EBV) antigens, remains
investigational.
Recommendations
• Surgery in form of nasopharyngectomy
should be considered as a first-line treatment
of residual or recurrent disease at the primary
site (R)
• Neck dissection remains the treatment of
choice for residual or metastatic neck disease
whenever possible (R)
• Re-irradiation should be considered as a
second line of treatment in recurrent disease
(R)
Treatment outcomes
Stages I and II
Five-year OS rates of 90 per cent for stage I and 84 per
cent for stage II have been reported from a review of
2687 patients from Hong Kong, based on the AJCC
1997 staging. Data for non-endemic regions are
sparse given the relative rarity of the condition in
these areas. Serum Epstein–Barr virus (EBV) DNA
copies before treatment have been shown to have prog-
nostic significance; for stages I and II <4000 copies
per ml have a 91 per cent survival at five years and
>4000 copies per ml have a 64 per cent five-year
survival.
Stages III and IV
Chemoradiotherapy regimes have improved the OS of
nasopharyngeal carcinoma (NPC) patients from 77 to
81 and 56 to 62 per cent at two and five years, respect-
ively. The benefit for chemotherapy was not lost for
advanced stage disease.
R SIMO, M ROBINSON, M LEI et al.
Recent studies using simultaneous integrated boost
delivered following neo-adjuvant chemotherapy with
IMRT, in locally advanced NPC, have suggested
local progression free and distant metastases free sur-
vival rates of 80–90 per cent. Accelerated RT sche-
dules or post-RT brachytherapy boost have produced
excellent local control rates, but more studies and
longer follow-up data are awaited to confirm the
benefits.
Patients with systemic metastases have been treated
with cisplatin containing regimes with response rates
ranging from 40 to 80 per cent, and median survival
of about 14 months.
Controversies
The role of ventilation tubes in the management of the
middle-ear effusion in nasopharyngeal cancer patients
The rate of complications (otalgia and otorrhoea) is
higher if grommets are inserted after RT. Eustachian
tube function may improve in an irradiated patient up
to five years after RT. However, if an effusion is
present or develops during RT tubal function remains
poor. Grommets bypass tubal obstruction, but may
exacerbate the inflammatory process. Up to 29 per
cent of patients will develop non-healing perforation
of the tympanic membrane, if grommets are inserted
during or after RT and 49 per cent will go onto
develop intermittent otorrhoea. Middle ear effusion
arising during or after RT is best managed using
repeated paracentesis, aspiration and a hearing aid.
Grommets should be used as a last resort.17,18
Salvage surgery for local recurrence
The maxillary swing nasopharyngectomy approach has
now been adopted as an adequate mode of salvaging
patients with recurrent nasopharyngeal carcinoma
(NPC) with survival rates of up to 73 per cent in
selected cases. The use of a purely endoscopic
approach has been attempted, without evidence of
any benefit. The controversy arises mainly on the
accurate assessment, patient selection and extent of
the resection, weighing the benefits of the procedure
against their morbidity.
Salvage treatments for recurrent disseminated disease
Isolated, potentially surgically treatable metastases in
NPC are rare and only limited reported cases specific
for NPC are available in the literature.
The role of neo-adjuvant and adjuvant chemotherapy
Recent meta-analyses have confirmed improvement in
local control but no improvement in OS. Recent
studies using neo-adjuvant chemotherapy followed
by concurrent chemoradiotherapy have produced
encouraging early results, but longer term data are
awaited.19,20
NASOPHARYNGEAL CARCINOMA: UK GUIDELINES
The use of routine tumour markers in the management
of NPC
Testing for Epstein–Barr virus (EBV) infection has
potential as a screening tool, but only in high risk
regions or populations. Epstein–Barr virus DNA
testing has also been used as diagnostic and prognostic
tool, and in the detection of recurrence. However, no
consensus exists on either the appropriate cut-off
values or the additional value to clinical management.
Key points
• Nasopharyngeal carcinoma is frequent in patients
of Southern China, Northern African and Alaskan
origin, but in western countries the adjusted inci-
dence is very low with only up to 1 per 100 000
• The most common signs and symptoms are nasal
obstruction, epistaxis, conductive hearing loss
secondary to otitis media with effusion, cranial
nerve neuropathies and cervical lymphadenopathy
• Intensity modulated radiotherapy, with or without
concurrent chemotherapy, is the mainstay of cura-
tive treatment, with concurrent chemotherapy for
stage III and IV disease
• A positron emission tomography–computed tom-
ography, computed tomography or magnetic res-
onance imaging scan should be carried out at
three months from completion of treatment to
assess response
• Salvage surgery should be considered for residual
or recurrent disease at the primary site
• Controversy exists in the management of otitis
media with effusion in patients with nasopharyn-
geal carcinoma, the best mode of salvage
surgery, salvage treatments for disseminated
disease, the use of neo-adjuvant and adjuvant che-
moradiotherapy and the use of tumour markers.
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2 Wei WI. Nasopharyngeal cancer: current status of management;
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3 Kam MK, Leung SF, Zee B, Chau RM, Suen JJ, Mo F et al.
Prospective randomized study of intensity-modulated radiother-
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carcinoma patients. J Clin Oncol 2007;25:4873–9
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peutic gain by changing from concurrent-adjuvant to induction-
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advanced nasopharyngeal carcinoma. Cancer 2015;121:
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8 Tham IW, Hee I, Yeo RM, Salleh PB, Lee J, Tan TW et al.
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ence. Int J Radiat Oncol Biol Phys 2009;75:1481–6
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Zelefsky MJ. Intensity-modulated radiation therapy (IMRT)
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Kettering experience. Int J Radiat Oncol Biol Phys 2006;64:
57–62
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locally recurrent nasopharyngeal carcinoma - A 10-year experi-
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Nasopharyngectomy for recurrent nasopharyngeal carcinoma:
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Endoscopic nasopharyngectomy for locally recurrent nasopha-
ryngeal carcinoma. Laryngoscope 2009;119:516–22
14 Lin CY, Tsai ST, Jin YT, Yang MW, Yeh IC, Hsiao JR.
Outcome of surgical management of persistent or recurrent
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et al. Reirradiation of locally recurrent nasopharynx cancer
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for recurrent and metastatic nasopharyngeal cancer. Jpn J Clin
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Address for correspondence:
Ricard Simo,
Department of Otolaryngology – Head and Neck Surgery,
Guy’s and St Thomas’ Hospital NHS Foundation Trust,
King’s and St Thomas’ Medical and Dental School,
London, UK
E-mail: ricardsimo1@icloud.com
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S104–S110. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000529

Hypopharyngeal cancer: United Kingdom National

Multidisciplinary Guidelines

P PRACY1, S LOUGHRAN2, J GOOD3, S PARMAR4, R GORANOVA5

1
Department of ENT/Head and Neck Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, 2University
Department of Otolaryngology, Manchester Royal Infirmary, Manchester, 3Department of Oncology, University
Hospitals Birmingham NHS Foundation Trust, Birmingham, 4Department of Oral and Maxillofacial Surgery,
University Hospitals Birmingham NHS Foundation Trust, Birmingham, and 5Northern Centre for Cancer Care,
Newcastle upon Tyne Hospitals, Newcastle upon Tyne, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. With an age standardised incidence rate of 0.63 per 100 000 population, hypopharynx
cancers account for a small proportion of the head and neck cancer workload in the UK, and thus suffer from
the lack of high level evidence. This paper discusses the evidence base pertaining to the management of
hypopharyngeal cancer and provides recommendations on management for this group of patients receiving
cancer care.

Recommendations
• Cross-sectional imaging with computed tomography of the head, neck and chest is necessary for all patients;
magnetic resonance imaging of the primary site is useful particularly in advanced disease; and computed
tomography and positron emission tomography to look for distant disease. (R)
• Careful evaluation of the upper and lower extents of the disease is necessary, which may require contrast
swallow or computed tomography and positron emission tomography imaging. (R)
• Formal rigid endoscopic assessment under general anaesthetic should be performed. (R)
• Nutritional status should be proactively managed. (R)
• Full and unbiased discussion of treatment options should take place to allow informed patient choice. (G)
• Early stage disease can be treated equally effectively with surgery or radiotherapy. (R)
• Endoscopic resection can be considered for early well localised lesions. (R)
• Bulky advanced tumours require circumferential or non-circumferential resection with wide margins to account
for submucosal spread. (R)
• Offer primary surgical treatment in the setting of a compromised larynx or significant dysphagia. (R)
• Midline lesions require bilateral neck dissections. (R)
• Consider management of silent nodal areas usually not addressed for other primary sites. (G)
• Reconstruction needs to be individualised to the patients’ needs and based on the experience of the unit with
different reconstructive techniques. (G)
• Consider tumour bulk reduction with induction chemotherapy prior to definitive radiotherapy. (R)
• Consider intensity modulated radiation therapy where possible to limit the consequences of wide field
irradiation to a large volume. (R)
• Use concomitant chemotherapy in patients who are fit enough and consider epidermal growth factor receptor
blockers for those who are less fit. (R)

Introduction sites in the head and neck, the overwhelming majority

The hypopharynx is subdivided into the piriform
sinuses, the posterior pharyngeal wall and the post-
cricoid area. The majority of cancers arise in the piri-
form sinuses (65–85 per cent), 10–20 per cent arise
from the posterior pharyngeal wall and 5–15 per cent
from the post-cricoid area. As is the case at other
(95 per cent) of cancers are squamous cell carcinomas
(SCCs). Five-year survival is poor with overall survival
at 30 per cent, although for T1 and T2 tumours the sur-
vival is almost 60 per cent. This discrepancy is a reflec-
tion of late presentation, as hypopharynx tumours
remain relatively asymptomatic until they are quite
HYPOPHARYNGEAL CANCER: UK GUIDELINES
advanced. Cases of T1N0 account for only 1–2 per cent
of all cases seen and 80 per cent of patients are stage III
or IV at presentation. Half of all patients present
because of cervical nodes and the incidence of distant
metastases at presentation are higher than that for any
other head and neck cancer.
Clinical presentation
The cardinal symptoms of hypopharyngeal cancer are:
• Neck mass, with approximately half of patients
presenting such, which reflects the fact that late
presentation is common
• Sore throat, particularly if well localised and asso-
ciated with referred ear pain on swallowing
• Dysphagia, which is progressive and frequently
results in significant weight loss and malnutrition
• Hoarseness, voice change and/or upper airway
obstruction, a late symptom indicating advanced
disease.
Assessment and staging
Clinical examination
Assessment of hypopharyngeal cancer requires a full
symptomatic history, evaluation of associated medical
conditions or comorbidity, determination of weight
loss as well as performance status (Karnofsky or
World Health Organization). The medical history and
performance status are critical in recommending the
extent and intention of treatment. Mortality and mor-
bidity rates are much higher in patients with significant
weight loss, comorbidity or poor performance
indicators.
A full head and neck examination, including nasen-
doscopy, is necessary in order to assess the size and
position of the primary tumour, mobility of the vocal
fold and cervical metastases. Clinical examination is
also important in assessment of pre-vertebral fascia
involvement and can be assessed by examining laryn-
gopharyngeal mobility in the lateral direction. This is
then complemented by radiological assessment and
staging endoscopy under general anaesthetic.
Imaging considerations
It is widely agreed that imaging is better performed
prior to biopsy, as this can potentially avoid post-opera-
tive oedema which may overstage the disease on subse-
quent imaging. In addition, it allows assessment of any
additional abnormalities that have been uncovered by
radiological evaluation such as second primary
tumours.
Cross-sectional imaging is mandatory in the work up
and can take the form of either computed tomography
(CT) or magnetic resonance imaging (MRI). In add-
ition to this, the chest should always be imaged due
to the increased incidence of lung metastases in
advanced hypopharyngeal cancer and to look for
S105
synchronous primaries. There is debate about which
modality to use. The critical points in imaging are
assessing extent of disease (particularly the lower
limits of the primary cancer) and the presence of
thyroid cartilage invasion. Magnetic resonance
imaging gives better soft tissue definition and has
greater sensitivity (80 per cent) for cartilage invasion,
however, is less specific (74 per cent) than CT, and
can therefore potentially overstage disease. The multi-
planar capabilities of MR can also help in staging the
disease. When compared with histological assessment,
CT and MRI produce sensitivities of 66 and 89 per
cent, respectively, and specificities of 94 and 84 per
cent, respectively. The benefit of CT is that the chest
can be imaged at the time of the neck imaging as
well as the reduced potential for motion artefact due
to the speed of the assessment, whereas, if MRI is
used the patient needs additional imaging which may
be less convenient for the patient. There is debate
whether or not a simple chest X-ray is sufficient or
whether CT is necessary. There is evidence to
support both arguments, however, as hypopharyngeal
cancer usually presents with stage III or IV diseases,
it seems reasonable to recommend chest CT, as there is
a higher incidence of distant metastatic disease in hypo-
pharyngeal cancer.
Currently, the Royal College of Radiologists 2014
guidelines recommends CT or MRI scanning for
imaging the hypopharynx.1 Computed Tomography
should use slice thickness acquired at 0.625–1.25 mm
and reformatted at no greater than 2.5 mm for viewing.
Scans should be performed during quiet respiration
with arms at the side of the patient. Patients should be
instructed not to swallow during the evaluation.
Magnetic resonance imaging scanning will require a
combination of axial, sagittal and coronal T1W and
T2W sequences, often with contrast enhancement with
spectral fat suppression to assess the extent of soft
tissue involvement and cartilage invasion.
Positron emission tomography (PET)–CT is now
recommended for assessment of advanced hypophar-
yngeal primaries, the lower limit of disease in cases
not accessible via endoscopy as well as in imaging
post-treatment patients to assess for residual and/or
recurrent disease.
Examination under anaesthetic and endoscopy
Endoscopy in theatre serves three functions: first, it
allows assessment of the extent of the primary
tumour, second, it allows biopsy of the tumour to
confirm pathology and finally it allows assessment of
other potential primary sites. This last indication was
the rationale of the old fashioned triple endoscopy phil-
osophy which incorporated bronchoscopy as well as
pharyngolaryngoscopy and oesophagoscopy. It is gen-
erally recognised that with the advent of good imaging
of the chest the role of formal bronchoscopy has
become virtually obsolete.
S106
TABLE I
T STAGING FOR HYPOPHARYNGEAL TUMOURS
Tx Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tis Carcinoma in situ
T1 Tumour limited to one subsite of the hypopharynx and
2 cm or less in greatest dimension
T2 Tumour invades more than one subsite of the hypopharynx
or an adjacent site, or measures more than 2 cm but 4 cm
or less in greatest diameter without fixation of
hemilarynx
T3 Tumour measures more than 4 cm in greatest dimension or
with fixation of hemilarynx
T4a Tumour invades thyroid/cricoid cartilage, hyoid bone,
thyroid gland, oesophagus or central compartment soft
tissue, which includes pre-laryngeal strap muscles and
subcutaneous fat
T4b Tumour invades pre-vertebral fascia, encases carotid artery
or involves mediastinal structures
At the end of all these assessments then a clinical
stage can be reached using the tumour–node–meta-
stasis (TNM) classification system (Table I).
Recommendations
• Cross-sectional imaging with CT of the head,
neck and chest is necessary for all patients;
MRI of the primary site is useful particularly
in advanced disease; and CT–PET to look for
distant disease (R)
• Careful evaluation of the upper and lower
extents of the disease is necessary, which may
require contrast swallow or CT–PET
imaging (R)
• Formal rigid endoscopic assessment under
general anaesthetic should be performed (R)
Management
High importance should be placed on exploring patient
preferences and involving them in treatment decisions.
A clear and unbiased discussion of all options will help
the patients and the medical team make the most
appropriate decisions. Many of these patients present
with dysphagia and significant weight loss and can
be profoundly malnourished. This needs to be
managed proactively soon after diagnosis and may
require insertion of nasogastric or gastrostomy
feeding tubes prior to any treatment taking place. A
full assessment of the patient’s performance status
should be carried out to determine their ability to
undergo major surgery or their ability to lie flat for
radiotherapy and attend daily for seven weeks.
Although some prospective randomised data exists,
several aspects of the decision making for hypophar-
yngeal SCC remain controversial as no treatment has
been shown to be superior in terms of disease
control and survival.2 This section summarises the
P PRACY, S LOUGHRAN, J GOOD et al.
principles of surgical and non-surgical treatment for
these tumours.
Recommendations
• Nutritional status should be proactively
managed (R)
• Full and unbiased discussion of treatment
options should take place to allow informed
patient choice (G)
Surgical treatment
Based on the extent of the tumour, transoral and open
surgical options exist for hypopharyngeal cancer.3
Transoral approaches have a greater ability to preserve
function suitable for smaller tumours where resections
can be achieved with clear margins. Radiation therapy
is favoured over open partial pharyngeal resections
nowadays.
Early stage disease. Early stage (I and II) disease can be
treated with equal effectiveness with surgery or radi-
ation.4,5 Early lesions of the hypopharynx can be
treated by transoral resection or open partial laryngo-
pharyngectomy with or without reconstruction.
Surgery offers the advantage of providing prognostic
information, such as peri-neural or angioinvasion and
lymph node status. This allows the use of post-opera-
tive irradiation for those patients likely to gain the
most benefit, while sparing other patients side effects
without a significant survival advantage. Occult
nodal disease is present in 30–40 per cent of patients,
so any treatment plan should include elective treatment
of the cervical nodes.
Late stage disease. Unfortunately, more than 80 per cent
are advanced stages III and IV at presentation (with
locally advanced disease present in the majority).
Submucosal extension is present in more than 60 per
cent of surgical specimens and is occult in one-third.6
Local recurrence rates have been reported to occur in
equal proportion between patients with negative
margins and those with positive margins, underscoring
the difficulty in clearing disease. Histological studies
have reported submucosal extension ranging from 1
to 2 cm, resulting in the recommendation that
minimal resection margins of 1.5 cm superiorly, 3 cm
inferiorly and 2 cm laterally are required in patients
treated surgically. The incidence and extent of sub-
mucosal spread is higher in patients who have under-
gone previous radiotherapy, with macroscopically
undetected submucosal spread present in 80 per cent.
Bulky advanced tumours will usually require circum-
ferential or non-circumferential resection with free
flap cover.
Recurrent disease. Surgical salvage after failure of
irradiation therapy has a lower success rate for
HYPOPHARYNGEAL CANCER: UK GUIDELINES
hypopharyngeal cancer than at any other site in the
head and neck, and larynx preservation is rarely pos-
sible.7 Patients who have undergone previous irradi-
ation require even greater resection margins.
Recommendations
• Early stage disease can be treated equally
effectively with surgery or radiotherapy (R)
• Endoscopic resection can be considered for
early well localised lesions (R)
• Bulky advanced tumours require
circumferential or non-circumferential
resection with wide margins to account for
submucosal spread (R)
• Offer primary surgical treatment in the
setting of a compromised larynx or significant
dysphagia (R)
Management of the neck. Midline lesions, those involv-
ing the posterior pharyngeal wall or post-cricoid area,
and lesions of the medial wall of the piriform sinus,
require bilateral neck dissection or irradiation,
because of a higher incidence of failure in the contralat-
eral neck. In surgically treated patients with a clinically
N0 neck, unilateral or bilateral neck dissection is war-
ranted, depending on the site and size of the primary.
In the clinically positive neck, a modified radical
neck dissection or a selective neck dissection on one
or both sides should be considered. Due attention
must be given to nodal involvement of the ‘silent
nodal areas’ – retropharynx, parapharynx, paratracheal
and mediastinum.
Recommendations
• Midline lesions require bilateral neck
dissections (R)
• Consider management of silent nodal areas
usually not addressed for other primary sites
(G)
Reconstruction. Reconstruction of pharyngeal defects
and in particular circumferential defects present major
challenges. Modern chemoradiotherapy protocols,
medical comorbidity and poor nutritional status
increase surgical morbidity. The aims of reconstruction
are to restore swallowing and speech, keeping mortality
and morbidity, in particular fistula and stricture rates, to
a minimum.
Partial pharyngeal defects. Partial pharyngeal defects
with more than 3.5 cm of unstretched remaining pha-
ryngeal mucosal width may be closed primarily.
S107
Defects with less than 3.5 cm of pharyngeal mucosal
width remaining may be reconstructed using a pedicled
flap – usually a pectoralis major flap. Free flaps, such
as the radial forearm flap and the anterolateral thigh
flap may also be used. These reconstructions are also
called ‘patch’ grafts. If the pharyngeal mucosal
remnant is very narrow (<1 cm in width), some sur-
geons would recommend excision of the remnant and
undertaking a total circumferential reconstruction.
However, many surgeons preserve this remnant and
reconstruct around it as it may reduce the stricture rate.
Total circumferential pharyngolaryngectomy defects.
Lower anastomosis above the clavicles: Where the
lower anastomosis of a total circumferential pharyngo-
laryngectomy reconstruction would lie above the clav-
icle, several options exist: jejunal free flap (JFF),
gastro-omental free flap (GOFF), tubed radial forearm
free flap (RFFF) and a tubed anterolateral thigh free
flap (ALT).8 All the above options carry the risk of
free flap failure, anastomotic leaks, stricturing, donor
site morbidity, failure of voice rehabilitation, swallow-
ing problems and a small peri-operative mortality rate.
Previously untreated cases: jejunal free flaps have
been associated with poorer swallowing thought to be
due to uncoordinated peristalsis and wet sounding
speech. The RFFF is easy to tube but has donor site
issues related to the size of the flap required. Recent lit-
erature has suggested that in previously untreated cases,
ALTs tubed over a salivary bypass tube appear to
provide the lowest complication rates – with minimal
donor site morbidity, lower leak rates and lower sten-
osis rates.9 Good swallowing and voice rehabilitation
have been reported. However, many authors have not
been able to replicate results in the literature and con-
tinue to use the JFF. Use of a salivary bypass tube
appears to reduce the fistula rates in fasciocutaneous
flaps.
Post-chemoradiotherapy (salvage cases): In general,
reconstructive surgery using free flap surgery post-che-
moradiotherapy carries a higher risk of complications
due to the deleterious effects of chemoradiotherapy
on tissue vascularity and wound healing. In such
cases, limited case series suggest that the use of the
GOFF may have an advantage due to the availability
and vascularity of the omentum.10 The omentum can
be wrapped around the anastomotic site to decrease
the possibility of leakage and also improve the vascu-
larity of the overlying skin quality. Any of the other
options mentioned previously may also be used in the
salvage cases. In the patients at high risk of breakdown,
a pectoralis major flap may be used to reinforce the
anastomotic suture lines in the pharynx.
Lower anastomosis below the clavicles: If the resec-
tion extends below the clavicles, a gastric pull through
or colonic transposition flap may be used.11 Both these
techniques carry increased morbidity and mortality due
to the need to enter multiple visceral cavities. Gastric
pull through carries a mortality rate of 5–15 per cent,
S108
morbidity of 31–55 per cent and reported fistula rates
of 3–23 per cent. Colonic transposition carries
similar risks, and appears to be less commonly used.
It can however provide a higher cranial reach than
gastric pull through, and is therefore useful for
tumours that extend up high into the oropharynx.
Swallowing after reconstruction with fasciocut-
aneous flaps (RFFF and ALT) and GOFF is reported
to be superior to that after JFF reconstruction. There
is little literature on the outcome of speech rehabilita-
tion following free flap reconstruction of total pharyn-
geal defects. However, speech rehabilitation is thought
to be best when fasciocutaneous flaps are used to
reconstruct the pharynx. There is a question as to the
advisability of primary tracheoesophageal puncture in
these cases. It has been argued that the presence of a
puncture site and valve or catheter can increase the
chance of infection and flap failure, and for this
reason, many surgeons would recommend secondary
puncture once the patient has healed and received
their post-operative radiotherapy as indicated. Some
centres perform a puncture if there is a reasonable
distance between the lower anastomosis and the site
of the puncture. As there is no evidence to support
either position, it is best to decide on an individual
case basis and depending on the experience of the
team.
Recommendation
• Reconstruction needs to be individualised to
the patients’ needs and based on the
experience of the unit with different
reconstructive techniques (G)
Non-surgical management
Definitive radiotherapy is a potentially organ-sparing
alternative to surgery in the treatment of early SCC of
the hypopharynx. In combination with systemic
therapy, it also has a role in the curative management
of locally advanced cancers, although typically not
those in which the cartilage is extensively involved or
the function of both vocal cords significantly impaired.
Post-operative radiation or chemoradiation improves
locoregional disease control and overall survival in
the presence of well-established high-risk features
such as a positive margin or extra-capsular nodal exten-
sion of disease.12
There has been no randomised side-by-side compari-
son of surgery and radiotherapy in T1 and 2 N0 hypo-
pharyngeal cancer. In advanced cancers, prospective
trials have shown equivalent rates of local control and
survival when surgery and adjuvant treatment was
compared with primary non-surgical therapy.13 Given
that the risk of local or locoregional failure is greater
than that of distant metastases, cancers that prove
P PRACY, S LOUGHRAN, J GOOD et al.
radiation resistant are sometimes surgically salvage-
able. The choice of initial therapy is often driven by
pragmatic clinical factors such as age, performance
status, medical comorbidity and patient wishes as
well as more subjective considerations such as
tumour accessibility, local expertise or predicted func-
tional outcome after radiotherapy. A multidisciplinary
approach involving surgical and radiation oncologists,
speech and language therapists and clinical nurse spe-
cialists is required.
The lymphatic drainage of the hypopharynx and the
resulting significant risk of occult nodal disease at pres-
entation typically mandate extensive irradiation of at-
risk nodal groups as well as treatment of the primary
tumour site and clinically apparent nodes. Intensity
modulated radiation therapy (IMRT) is now well estab-
lished in UK radiotherapy centres. This technique, in
combination with adherence to consensus guidelines
regarding target volume delineation and sophisticated
imaging of patient position and anatomical changes
during radiotherapy, allows much more precise and
accurate targeting of tumouricidal radiation dose to
the target. Intensity modulated radiation therapy also
reduces radiation dose to organs at risk, such as the
parotid, resulting in reduced medium term toxicity.
There is also some evidence that patients treated with
IMRT rather than three-dimensional conformal radio-
therapy achieve higher rates of local control and
better functional outcomes. Intensity modulated radi-
ation therapy should therefore be considered the stand-
ard of care.
The predominantly loco-regional pattern of treat-
ment failure in hypopharyngeal cancer has generated
interest in treatment intensification, particularly in the
setting of locally advanced disease. Intensity modu-
lated radiation therapy has facilitated attempts at escal-
ation of radiation dose. The addition of concomitant
systemic therapy in the form of cisplatin (or cetuximab
in patients with contraindications such as impaired
renal function) confers a modest improvement overall
survival at the expense of increased acute toxicity.
All but the least fit patients under the age of 71 with
stage III or selected stage IV disease should therefore
be considered for combination treatment. Patients
aged 71 or more were shown in the meta-analysis of
chemotherapy in head and neck cancer to be unlikely
to benefit from the addition of systemic therapy.14,15
The optimal use of induction chemotherapy in hypo-
pharyngeal cancer, as in other anatomical subsites,
remains a topic of discussion. Two large trials have
demonstrated its utility in an organ preservation
approach with comparable survival to surgery in laryn-
geal cancer. Induction therapy reduces the incidence of
distant metastases but does not have a consistent effect
on overall survival, although individual studies com-
paring induction schedules with and without a taxane
have shown a significant benefit for triple-agent
chemotherapy.16 One pragmatic approach is to offer
HYPOPHARYNGEAL CANCER: UK GUIDELINES
induction chemotherapy prior to chemoradiation to fit
patients with bulky T3 or early T4 disease,13 with lar-
yngectomy for those who do not respond to chemother-
apy, and to patients at high risk of distant relapse such
as those with N2b or c or N3 disease.
Recommendations
• Consider tumour bulk reduction with
induction chemotherapy prior to definitive
radiotherapy (R)
• Consider IMRT where possible to limit the
consequences of wide field irradiation to a
large volume (R)
• Use concomitant chemotherapy in patients
who are fit enough and consider EGFR
blockers for those who are less fit (R)
Palliative care
It has been estimated that up to 25 per cent of patients
are not suitable for curative treatment at presentation
because of age, the extent of locoregional disease,
distant metastases, comorbidity or refusal of surgery.
Following treatment, 50–60 per cent of patients
develop a recurrence in less than 12 months, and
most mortality in the first two years following diagno-
sis is due to locoregional recurrence. The overall five-
year disease specific survival rate is approximately
30–35 per cent with five-year survival rates of 14–22
per cent for stage IV disease. Volume of disease and
laryngeal involvement adversely impact survival.
Combination chemotherapy has been shown to
improve overall survival.17
Patients with hypopharyngeal cancer may suffer
from severe symptoms; including pain, swallowing dif-
ficulties, aspiration, chest infections, anorexia and
weight loss. In many cases, symptoms will have been
aggravated by previous treatments; surgery, radiation
and chemotherapy (mucositis, hypopharyngeal sten-
osis, infections, pharyngocutaneous fistula, psycho-
logical distress and cachexia). All of these require
attention and some may be relieved by surgical inter-
ventions such as tracheostomy and the insertion of a
gastrostomy to relieve breathing and restore hydration
and nutrition.
Some patients, with minimal local symptoms are
suitable for targeted agents in recurrent local and/or
metastatic disease. These are highly selected patients
and palliative treatments should be discussed and
offered to patients through the multidisciplinary team
(MDT). Patients with symptomatic lung metastases
are often those who benefit most from palliative
chemotherapy. Palliative radiotherapy may be used
for patients, unsuitable for curative treatment, who
present with bleeding or uncontrolled pain from the
hypopharynx and can be excellent for cutaneous metas-
tases, painful lymph nodes or bony disease.
S109
Key points.
• The majority of cancers arise in the piriform
sinuses (65–85 per cent), 10–20 per cent arise
from the posterior pharyngeal wall and 5–15 per
cent from the post-cricoid area
• Patient choice and involvement in treatment deci-
sions is of high importance and a clear and
unbiased discussion of their options will help
them and their medical team make the most appro-
priate treatment decisions
• Primary non-surgical treatment is recommended
for most locally advanced tumours unless the
laryngeal function is compromised or significant
dysphagia exists
• Early stage (I and II) disease can be treated with
equal effectiveness with surgery or radiation
• Bulky advanced tumours will usually require cir-
cumferential or non-circumferential resection
with free flap cover
• Five-year survival is poor with overall survival at
30 per cent, although for T1 and T2 tumours the
survival is almost 60 per cent
• Up to 25 per cent of patients are not suitable for
curative treatment at presentation because of age,
the extent of locoregional disease, distant metasta-
ses, comorbidity or refusal of surgery.
References
1 Olliff J, Richards P, Connor S, Wong WL, Beale T, Madani G.
Head and neck cancers. In: Nicholson T, edn. Recommendations
for Cross-Sectional Imaging in Cancer Management. London:
The Royal College of Radiologists, 2014:3–19
2 Hall SF, Groome PA, Irish J, O’Sullivan B. Radiotherapy or
surgery for head and neck squamous cell cancer: establishing
the baseline for hypopharyngeal carcinoma? Cancer 2009;
115:5711–22
3 Bradley PJ. Cancer of the hypopharynx. Oper Tech Otolaryngol
2005;16:55–66
4 Eckel HE, Staar S, Volling P, Sittel C, Damm M, Jungehuelsing
M. Surgical treatment for hypopharynx carcinoma: feasibility,
mortality, and results. Otolaryngol Head Neck Surg 2001;124:
561–9
5 Martin A, Jackel MC, Christiansen H, Mahmoodzada M, Kron
M, Steiner W. Organ preserving transoral laser microsurgery
for cancer of the hypopharynx. Laryngoscope 2008;118:
398–402
6 Ho CM, Ng WF, Lam KH, Wei WJ, Yuen AP. Submucosal
tumor extension in hypopharyngeal cancer. Arch Otolaryngol
Head Neck Surg 1997;123:959–65
7 Godballe C, Jorgensen K, Hansen O, Bastholt L.
Hypopharyngeal cancer: results of treatment based on radiation
therapy and salvage surgery. Laryngoscope 2002;112:834–8
8 Patel RS, Goldstein DP, Brown D, Irish J, Gullane PJ, Gilbert
RW. Circumferential pharyngeal reconstruction: history, critical
analysis of techniques, and current therapeutic recommenda-
tions. Head Neck 2010;32:109–20
9 Murray DJ, Gilbert RW, Vesely MJ, Novak CB, Zaitlin-Gencher
S, Clark JR et al. Functional outcomes and donor site morbidity
following circumferential pharyngoesophageal reconstruction
using an anterolateral thigh flap and salivary bypass tube.
Head Neck 2007;29:147–54
10 Patel RS, Makitie AA, Goldstein DP, Gullane PJ, Brown D, Irish J
et al. Morbidity and functional outcomes following gastro-omental
free flap reconstruction of circumferential pharyngeal defects.
Head Neck 2009;31:655–63
11 Triboulet JP, Mariette C, Chevalier D, Amrouni H. Surgical
management of carcinoma of the hypopharynx and cervical
esophagus: analysis of 209 cases. Arch Surg 2001;136:1164–70
S110
12 Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J,
Forastiere A et al. Defining risk levels in locally advanced
head and neck cancers: a comparative analysis of concurrent post-
operative radiation plus chemotherapy trials of the EORTC
(#22931) and RTOG (# 9501). Head Neck 2005;27:843–50
13 Lefebvre JL, Andry G, Chevalier D, Luboinski B, Collette L,
Traissac L et al. Laryngeal preservation with induction chemo-
therapy for hypopharyngeal squamous cell carcinoma: 10-year
results of EORTC trial 24891. Ann Oncol 2012;23:2708–14
14 Blanchard P, Baujat B, Holostenco V, Bourredjem A, Baey C,
Bourhis J et al. Meta-analysis of chemotherapy in head and
neck cancer (MACH-NC): a comprehensive analysis by
tumour site. Radiother Oncol 2011;100:33–40
15 Pignon JP, le Maitre A, Maillard E, Bourhis J, Group M-NC.
Meta-analysis of chemotherapy in head and neck cancer
(MACH-NC): an update on 93 randomised trials and 17,346
patients. Radiother Oncol 2009;92:4–14
P PRACY, S LOUGHRAN, J GOOD et al.
16 Posner MR, Hershock DM, Blajman CR, Mickiewicz E,
Winquist E, Gorbounova V et al. Cisplatin and fluorouracil
alone or with docetaxel in head and neck cancer. N Engl J
Med 2007;357:1705–15
17 Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A,
Rottey S et al. Platinum-based chemotherapy plus cetuximab
in head and neck cancer. N Engl J Med 2008;359:1116–27
Address for correspondence:
Paul Pracy,
Department of ENT Head and Neck Surgery,
Queen Elizabeth Hospital Birmingham,
Birmingham, UK
E-mail: paul.pracy@uhb.nhs.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S111–S118. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000530

Nose and paranasal sinus tumours: United

Kingdom National Multidisciplinary Guidelines

V J LUND1, P M CLARKE2, A C SWIFT3, G W MCGARRY4, C KERAWALA5, D CARNELL6

1
Royal National Throat Nose and Ear Hospital, London, 2Department of ENT, Charing Cross and Royal Marsden
Hospitals, London, 3Aintree University Hospitals NHS Foundation Trust, Liverpool, 4Department of
Otolaryngology – Head and Neck Surgery, Glasgow Royal Infirmary, Glasgow, 5The Royal Marsden Hospital,
London, and 6Department of Oncology, University College Hospital, London, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. With only limited high-level evidence for management of nasal and paranasal sinus cancers
owing to low incidence and diverse histology, this paper provides recommendations on the work up and
management based on the existing evidence base.

Recommendations
• Sinonasal tumours are best treated de novo and unusual polyps should be imaged and biopsied prior to definitive
surgery. (G)
• Treatment of sinonasal malignancy should be carefully planned and discussed at a specialist skull base
multidisciplinary team meeting with all relevant expertise. (G)
• Complete surgical resection is the mainstay of treatment for inverted papilloma and juvenile angiofibroma. (R)
• Essential equipment is necessary and must be available prior to commencing endonasal resection of skull base
malignancy. (G)
• Endoscopic skull base surgery may be facilitated by two surgeons working simultaneously, utilising both sides
of the nose. (G)
• To ensure the optimum oncological results, the primary tumour must be completely removed and margins
checked by frozen section if necessary. (G)
• The most common management approach is surgery followed by post-operative radiotherapy, ideally within six
weeks. (R)
• Radiation is given first if a response to radiation may lead to organ preservation. (G)
• Radiotherapy should be delivered within an accredited department using megavoltage photons from a linear
accelerator (typical energies 4–6 MV) as an unbroken course. (R)

Introduction cavity and paranasal sinuses can be affected, but the

Tumours in the sinonasal region are rare, affecting less
than 1 in 100 000 people per year.1 They are histologi-
cally a diverse group of tumours and potentially pose
significant management problems due to their close
proximity to the orbit and intracranial cavity.
Squamous cell carcinoma (SCC) is the most common
malignant tumour, but tumours of every histological
type can occur. The commoner epithelial tumours
include adenocarcinoma, olfactory neuroblastoma,
malignant melanoma and adenoid cystic carcinoma.
Sarcomas, e.g. chondrosarcoma and rhabdomyosar-
coma and haemoproliferative tumours, e.g. lymphoma
may also occur.
Benign tumours include inverted papilloma (IP),
osteoma, juvenile angiofibroma (JA), haemangioperi-
cytoma, haemangioma, schwannoma, pleomorphic
adenoma and meningioma. All areas of the nasal
lateral wall, ethmoids and maxillary sinus are the
most common primary sites. The frontal and sphenoid
sinuses are rare primary sites for reasons that are
unknown.
Clinical presentation
Initial symptoms such as nasal blockage, blood-stained
discharge and loss of smell are often overlooked
though their unilateral nature should raise suspicion.
Delayed presentation is common. Subsequent exten-
sion into the orbit, nasolacrimal system, anterior
cranial cavity, cavernous sinus, pterygomaxillary
fissure, palate, skin and infratemporal fossa may
produce symptoms such as proptosis, diplopia and
epiphora, trismus, pain, oro-antral fistula, paraesthesia
or other neurological deficits or a mass.
S112
FIG. 1
Management algorithm for malignant sinonasal tumours.7
Assessment and staging
Investigation should include computed tomography
(CT) and magnetic resonance imaging (MRI) which
are complementary in the skull base, and biopsy
(Figure 1). Computed tomography scans give excellent
bony details and are helpful in determining whether a
tumour remains confined within these natural boundar-
ies or has eroded through the surrounding bone. They
also provide details of the extent of local bony invasion
and are useful in assessing the lamina papyracea,
orbital floor, cribriform plate and pterygoid plates.
Magnetic resonance imaging allows better distinction
of tumour from adjacent soft tissues and retained
mucus and is particularly useful for determining inva-
sion of the orbital contents, dura, brain and cavernous
sinus. An MRI may also be better for assessing
carotid artery invasion. Positron emission tomog-
raphy-computed tomography (PET-CT) imaging is uti-
lised where the tumour could be an unusual metastatic
site from a primary tumour elsewhere in the body, e.g.
adenocarcinoma or occasionally where widespread
metastatic disease is a clinical possibility, e.g. an
aggressive sarcoma. Table I shows the staging system
for nasal and paranasal sinus malignancies.2
Recommendations
• Sinonasal tumours are best treated de novo
and unusual polyps should be imaged and
biopsied prior to definitive surgery (G)
• Treatment of sinonasal malignancy should be
carefully planned and discussed at a specialist
skull base multidisciplinary team (MDT)
meeting with all relevant expertise (G)
V J LUND, P M CLARKE, A C SWIFT et al.
TABLE I
T STAGING FOR NASAL AND PARANASAL SINUS
TUMOURS (EXCEPT SINONASAL MALIGNANT
MELANOMA)
Maxillary sinus
T1 Tumour limited to the mucosa with no erosion or
destruction of bone
T2 Tumour causing bone erosion or destruction,
including extension into hard palate and/or
middle nasal meatus, except extension to
posterior wall of maxillary sinus and pterygoid
plates
T3 Tumour invades any of the following: bone of
posterior wall of maxillary sinus, subcutaneous
tissues, floor or medial wall of orbit, pterygoid
fossa, ethmoid sinuses
T4a Tumour invades any of the following: anterior
orbital contents, skin of cheek, pterygoid plates,
infratemporal fossa, cribriform plate, sphenoid
or frontal sinuses
T4b Tumour invades any of the following: orbital
apex, dura, brain, middle cranial fossa, cranial
nerves other than maxillary division of
trigeminal nerve V2, nasopharynx, clivus
Nasal cavity and ethmoid sinus
T1 Tumour restricted to one subsite of nasal cavity or
ethmoid sinus, with or without bony invasion
T2 Tumour involves two subsites in a single site or
extends to involve an adjacent site within the
nasoethmoidal complex, with or without bony
invasion
T3 Tumour extends to invade the medial wall or floor
of the orbit, maxillary sinus, palate or cribriform
plate
T4a Tumour invades any of the following: anterior
orbital contents, skin of nose or cheek, minimal
extension to anterior cranial fossa, pterygoid
plates, sphenoid or frontal sinuses
T4b Tumour invades any of the following: orbital
apex, dura, brain, middle cranial fossa, cranial
nerves other than V2, nasopharynx, clivus
Management
Discussion about management of these rare tumours
should ideally occur in a specialist skull base MDT.
Benign sinonasal tumours
Sinonasal inverted papilloma. Sinonasal IP is the most
common pathology and much of the literature on man-
agement of benign nasal tumours concerns itself with
IP.3 It is a locally aggressive tumour, which usually
arises in the nasal cavity. Inverted papilloma is asso-
ciated with a risk of malignant transformation (about
2 per cent) and it is known to carry a high risk of
post-treatment recurrence and/or residual disease if a
subperiosteal resection is not undertaken. Expert histo-
pathology review is essential as well differentiated SCC
can easily be mistaken for IP.
Juvenile angiofibroma. Juvenile angiofibroma is a slow
growing highly vascular tumour which arises predom-
inantly from the sphenopalatine region in adolescent
and young adult males. The tumour is locally invasive
and can cause life-threatening epistaxis. As with
inverted papilloma this lesion can extend to involve
NOSE AND PARANASAL SINUS TUMOURS: UK GUIDELINES
the sinuses, orbits and intracranial space. The basisphe-
noid is the commonest site of residual disease usually
due to invasion via the vidian canal.
Treatment. Despite differences in tumour behaviour
across the range of pathologies, all share the same
basic treatment aims of complete surgical removal
without damage to adjacent organs and with prevention
of recurrence.
The mid-facial degloving approach has been the
mainstay for access if the frontal sinus or anterior eth-
moids are not involved. Complex frontal tumours and
those with intracranial extension have required use of
osteoplastic flap and craniofacial approaches. In a
large series of open surgery for inverted papilloma,
an overall recurrence rate of 17 per cent is found. For
juvenile angiofibroma, ‘recurrence’ rates fell from 21
to 2 per cent when drilling of the basisphenoid was
employed during midfacial degloving. More recently,
endoscopic surgery and endoscope assisted, minimal
access surgery (see below) are more often employed,
having been shown to be effective alternatives with
equivalent results and reduced morbidity compared to
open approaches.4
Recent studies of endoscopic surgery for inverted
papilloma suggest recurrence rates of around 14 per
cent are achievable by experienced endoscopic sur-
geons. A similar recurrence rate has been reported for
juvenile angiofibroma resected endoscopically though
the series are relatively small.
Recommendation
• Complete surgical resection is the mainstay of
treatment for inverted papilloma and juvenile
angiofibroma (R)
Malignant sinonasal tumours
Surgical approaches (Figure 2)
Endoscopic resection of sinonasal tumours. The
accepted method of resecting tumours of the anterior
skull base is craniofacial resection.5 However, recent
technological advances have facilitated endoscopic
resection of malignant tumours of the lateral nasal
wall and anterior skull base with safety and
precision.6–9
In some cases, tumour resection may be entirely
endoscopic, but the endoscope may also be combined
to enhance surgical resection with craniotomy, mid-
facial degloving and lateral rhinotomy. Patients with
sinonasal malignancy undergoing purely endonasal
resection are reported to have outcomes as good as con-
ventional external surgical techniques with the potential
for lower morbidity and shorter hospital stays.
Endoscopic resection of sinonasal tumours should be
managed in units that have comprehensive skull base
expertise that can manage all facets of the patient’s care.
S113
FIG. 2
Management algorithm for malignant sinonasal tumours
continued.7
Indications for endoscopic endonasal resection.
Prior to undertaking this means of treatment, a clear
operative plan must be considered by an MDT with
the full range of expertise in the management of sino-
nasal malignancy. Surgeons undertaking endoscopic
resection must be experienced in both endoscopic tech-
niques and the full range of other surgical options with
which they may be combined and must also be familiar
with the natural history of the wide range of malignant
sinonasal tumours. Once a decision has been made to
treat a tumour surgically, the clinician should define
whether this is with curative intent or palliation.
Contraindications to endoscopic resection
(Table II): Tumours invading facial soft tissues
should not be attempted endoscopically.
Tumours that are very vascular would pose a consid-
erable problem if resected endoscopically. Embolisa-
tion within days of definitive surgery should be
considered in these cases. Relative contraindications
to endoscopic resection include extension to the
orbital apex or laterally to the pterygomaxillary space
and infratemporal fossa. Malignant tumour invasion
of the cavernous and sagittal sinuses and brain paren-
chyma is difficult to clear endoscopically, but a deci-
sion to operate under these circumstances would
mainly be for palliation rather than cure.
Surgical considerations. Intra-operative computer
assisted navigation should ideally be available. Some
systems incorporate CT–MR fusion and three-dimen-
sional CT angiography. Powered instruments should
also include a microdebrider and high-speed drill
systems with long diamond burrs and curved drills
designed for intranasal use. Diathermy instruments
designed for endoscopic intranasal use should be avail-
able, bipolar diathermy being preferable. Resecting
tumours endoscopically is aided by having two sur-
geons using a 3–4 handed technique via both sides
of the nose. This technique is facilitated by partial exci-
sion of the nasal septum. En bloc resection is usually
not possible in the skull base. The most important prin-
ciple is to obtain clearance of tumour usually by
S114
TABLE II
LIMITATIONS OF ENDOSCOPIC SURGERY WITH
CURATIVE INTENT7
Absolute
When the following are required:
Orbital exenteration
Maxillectomy (except medial wall)
Skin excision
Anterior +/or lateral involvement of frontal sinus
Dura or brain involvement lateral to mid orbital roof or lateral to
optic nerve
Brain parenchyma invasion
Vascular invasion (internal carotid artery, cavernous sinus)
Chiasm invasion
piecemeal resection, confirmed with frozen section
when necessary. The extent of resection is determined
by the histology: for olfactory neuroblastoma, the olfac-
tory bulbs and tracts may be resected, but for high grade
malignancy invading critical structures such as the cav-
ernous sinus, complete resection is not possible. The
incidence of positive tumour-margins is reported to be
similar in patients with advanced anterior skull base
disease undergoing either endoscopic resection or trad-
itional craniofacial resection. Dura may be resected if
invaded by tumour, but if extensive, an open approach
may be more suitable. Reconstruction of the skull base
defect is essential at the time of the primary surgery if
the skull base or dura have been included in the resec-
tion. A multilayered technique is recommended and
graft materials include autologous fascia, cartilage, fat,
split calvarial bone and local mucosal flaps and grafts.
Large pedicled septal mucosal flaps based on the sphe-
nopalatine artery have been described, but are only suit-
able if the mucosa is not invaded by the tumour.
Recommendations
• Essential equipment is necessary and must be
available prior to commencing endonasal
resection of skull base malignancy (G)
• Endoscopic skull base surgery may be
facilitated by two surgeons working
simultaneously, utilising both sides of the
nose (G)
• To ensure the optimum oncological results,
the primary tumour must be completely
removed and margins checked by frozen
section if necessary (G)
Results. Five-year disease-specific survival rates of
85 per cent after endoscopic resection of sinonasal
malignancy are reported though selection bias needs
to be taken into account.10,11 Encouraging results
with good local control are reported following the
endoscopic resection of olfactory neuroblastoma.12,13
V J LUND, P M CLARKE, A C SWIFT et al.
The overall survival of adenocarcinoma after endo-
scopic resection is reported at 92 per cent with a
median follow-up of 30 months. The results following
endoscopic resection of SCC are significantly worse.
The outcome is dependent on the histology of the
primary tumour as well as the presence of intracranial
spread and positive surgical margins. With more
recent larger series, survival is worse with increasing
T-stage with the exception of malignant melanoma.14
However, endoscopic resection of melanoma is asso-
ciated with improved five-year survival (though not
10-year survival) irrespective of extent. Survival is
best for patients who have not undergone previous
surgery with incomplete resection.
Maxillectomy. Maxillary tumours represent 3 per cent
of all head and neck tumours. Of these tumours, 75 per
cent are malignant. Of the malignant tumours, 80 per
cent are of epithelial origin, with the remainder being
most commonly salivary gland (adenoid cystic
carcinoma > muco-epidermoid carcinoma > adenocar-
cinoma), malignant melanoma or sarcomas. There is a
slight male preponderance, with most tumours occurring
in the fifth and sixth decades. The five-year survival is
between 30 and 50 per cent.
Pre-operative planning It is important that a clear
reconstructive plan is derived for the maxillectomy
defect prior to surgery with a decision to either obturate
the cavity with a prosthesis or perform some form of
biological reconstruction. The latter includes local or
regional flaps in addition to free-tissue transfer of a
soft tissue only or composite nature. Ultimately the
decision will depend on competing factors such as
the site and size of the defect, available dentition
after resection, concurrent comorbidity and prognosis.
The reconstructive and prosthetic aspects of maxillect-
omy rehabilitation are dealt with in greater detail else-
where in these guidelines. In summary, obturators have
the advantage in that they reduce the length of surgery,
impart no additional donor site morbidity, restore the
dentition more immediately and theoretically retain
the ability to inspect the post-ablative cavity, although
in the era of PET–CT the latter argument is declining.
However, obturators have their disadvantages. In
the short term, this includes the need for frequent
changes initially under general anaesthesia along with
the requirement for repeated adjustment and refashion-
ing as the maxillectomy cavity settles down. In the
longer term, obturators impart more discomfort and
demand patient compliance to remove and clean
them. Studies that compare obturators with biological
reconstruction demonstrate improved quality of life
metrics for the latter group and as such the standard
of care is to favour appropriate vascularised flap recon-
struction as discussed elsewhere in these guidelines
unless patient preferences or other contraindications
exist.
Surgical technique. Access to the maxilla may
be transoral, transcutaneous or extended. The trans-
NOSE AND PARANASAL SINUS TUMOURS: UK GUIDELINES
oral route can be supplemented with a mid-facial
degloving procedure. The transcutaneous incision
(Weber–Ferguson) involves division of the upper lip
and extension around the nasal vestibule and alar of
the nose towards the medial canthus. Additional expos-
ure of the ethmoid sinuses may be aided with a
Lynch extension. Likewise access to the lateral and
posterior-lateral maxilla may be improved with a trans-
conjunctival, subciliary or infra-orbital extension. Skin
flaps are raised in a submuscular plane to maintain
blood supply and also minimise damage to the facial
nerve. It is important to ensure adequate exposure by
elevating skin flaps as far back as the posterior-lateral
surface of the maxilla and under the surface of the
zygoma in order to gain adequate access to the pterygo-
palatine fissure. Bony osteotomies are performed
through tooth sockets or edentulous areas with either
drills or saws. After the osteotomies are completed
the specimen is delivered with division of the posterior
soft tissue attachments. Care should be taken here to
avoid bleeding from the palatine vessels and branches
of the maxillary artery. The infra-orbital nerve can
only be preserved if a low maxillectomy is performed.
Management of the orbit is discussed below. If imme-
diate obturation is to be carried out, it is imperative that
the ablative cavity is adapted. Sharp spicules of bone
should be removed, but undercuts retained to aid reten-
tion of the prosthesis. If obturation is to be performed, a
simultaneous coronoidectomy should be carried out.
Craniofacial resection. Approaches. Type 1 craniofa-
cial or transorbital cranial facial uses the lateral rhinot-
omy incision extended up into a Lynch incision. There
is no need to extend this incision around the nasal alar
so avoiding any asymmetry of the alar base. Wide
release of the orbital periosteum and lacrimal duct
allows gentle lateral reflection of the orbital contents
giving excellent exposure of the ethmoids and cribri-
form plate, lateral nasal wall, fronto-nasal recess,
lamina papyracea and orbital periosteum all of which
can be resected. Small areas of ethmoidal roof, cribri-
form plate and the olfactory bulb can be resected
from below and dura resected and repaired as neces-
sary. Type 2 craniofacial includes a shield shaped
window craniotomy over the frontal sinus allowing
excellent exposure of the superior surface of the cribri-
form plates allowing en bloc resection of dura, cribri-
form plate and early brain involvement. It allows
robust repair of the dura under direct vision with
fascia lata or pericranium. Type 3 craniofacial involves
an approach to the ethmoids via a lateral rhinotomy-
type incision and a large frontal craniotomy approached
by a bicoronal incision. This is only required for sig-
nificant intracranial disease requiring neurosurgical
input.
Orbital management. An understanding of the ana-
tomical barriers to the disease is very important. Both
the dura and the orbital periosteum provide significant
barriers. In particular the orbital periosteum may still be
S115
intact despite considerable intra-orbital tumour with
proptosis. Although care must be taken to avoid
attempting orbital preservation at the potential cost of
decreased local disease control and survival, at
present the most commonly performed approach with
frozen section control is to resect involved orbital peri-
osteum and preserve the orbital contents in cases where
there is no invasion through the periosteum into orbital
fat, orbital musculature or orbital apex. There does
however remain some debate about the oncological
basis for this. Although the loss of an eye psychologic-
ally is often very difficult for patients to consider, it
must be remembered that preservation of a painful
eye with diplopia and poor vision following RT is a sig-
nificantly worse outcome than orbital clearance with an
excellent prosthesis.
Contraindications to surgery. Anatomical areas
which preclude surgical intervention differ with the
aggressiveness of the pathology. An aggressive
tumour invading the cavernous sinus, particularly if it
reaches the internal carotid artery or with massive
intra-cranial extension, would be deemed incurable
and the morbidity of surgical intervention would out-
weigh any potential benefits. These, however, are prob-
ably the only anatomical contraindications to surgery.
With slower growing tumours quite significant intracra-
nial disease may well still be amenable to surgical inter-
vention with a hope of long-term survival. Significant
involvement of both eyes or the loss of an only
seeing eye is a devastating consequence of surgery
and this would be a relative contraindication to any sur-
gical resection.
Regional nodes. Lymph node involvement at diagno-
sis is low. Rates are higher with increasing T stage, and
squamous and undifferentiated histology. In T3–T4
SCC maxillary tumours elective nodal treatment of
ipsilateral levels Ib and II has been advocated. In con-
trast, ethmoid sinus tumours have been associated with
low rates of both lymph node involvement at diagnosis
and nodal recurrence (approximately 2 and 7 per cent,
respectively).
Olfactory neuroblastoma can be associated with
lymphatic spread, both uni- and bi-lateral in up to 25
per cent of cases.15
Results. Results from combined surgery and RT are
very dependent on pathology and the anatomical
areas involved by tumour with results if orbit and
brain are involved being extremely poor. Involvement
of the periorbita or dura also reduces survival. The fol-
lowing figures indicate published five years overall sur-
vival for common histological variants: SCC 30–55
per cent, adenocarcinoma 45–60 per cent and olfactory
neuroblastoma approximately equal to 75 per cent.
Radiation therapy
Role of RT. Sino-nasal tumours are often advanced at
presentation, invading adjacent structures and lie in
S116
close proximity to many organs at risk of damage from
radiation (lens, retina, optic nerve and chiasm, brain
tissue, pituitary gland). This makes irradiation to a
radical dose difficult.16 The added numerous air-
tissue interfaces within the treated volume also make
for inhomogeneous dose absorption and efforts
should be made to eliminate these using tissue bolus
techniques where possible. If orbital or brain invasion
occurs, survival rates are extremely poor despite
aggressive treatment.
The most common management approach is surgery
followed by post-operative RT, although some proto-
cols have used chemotherapy alongside, where the
tumour is recognised to be chemosensitive, e.g. SCC
(Figure 2).
Following surgery that involves a dural repair a
longer interval before RT may be preferred to allow
healing. The sequence of surgery and RT remains
open to debate, with no significant differences in
outcome found.
Pre-operative (chemo) RT may allow for less exten-
sive surgery in advanced tumours.
The implementation of new advanced radiation tech-
niques such as intensity modulated radiotherapy
(IMRT) is especially attractive in sinus tumours as
the dose distributions achieved with conventional tech-
niques are rather inhomogeneous, with areas of low
dose that can potentially contribute to local recur-
rence.17 IMRT has demonstrated improved coverage
of the tumour bed and potential sites of spread,
whilst ensuring levels of radiation exposure are kept
within the tolerance of adjacent neurological structures.
Prospective studies with mature outcome data are not
yet available.
Dose escalation above conventional dose levels is
achievable with IMRT and this will be an active area
of future study to improve local control, since the
majority of local failures occur within the radiation
field. Patients with the most advanced tumours, previ-
ously thought to be suitable only for palliation, may
then become treatable radically.
Proton therapy is currently under evaluation and may
have a role in treating small volume disease, e.g. low
grade tumours at the skull base or close to radiosensi-
tive structures, due to rapid dose fall off. It has been
used in chondrosarcoma and olfactory neuroblastoma
is included in the recommendations for specialised ser-
vices in paediatric oncology. Sub-volumes may also be
potentially treated using protons as a boost to residual
tumour masses within a larger photon field as mixed
plans.
Radiation toxicity. Doses delivered with conventional
RT are of the order of 60–70 Gy and are known to
cause blindness in up to a third of patients, and too
often sacrifice of the sight in one eye is unavoidable.18
Care must be taken to avoid a dry eye, caused by radi-
ation injury from quite modest doses to the lacrimal
V J LUND, P M CLARKE, A C SWIFT et al.
gland (30 Gy), as optic pain, perforation and even enu-
cleation may ensue.
Brain radionecrosis is a potentially devastating com-
plication of RT and the risk depends on the total dose,
dose per fraction, overall treatment time and volume,
with tolerance for partial volume irradiation set at
55–60 Gy/30 fraction equivalent dose. There is,
however, very little information on the effect of irradi-
ating large volumes of tissue to lower doses as occurs
with IMRT, due to the multiple radiation portals.
Conventional dose prescriptions include 60–70 Gy
in 30–35# over 6 to 7 weeks for SCC, adenocarcinoma,
undifferentiated carcinoma and olfactory neuroblast-
oma. Doses for lymphoma are approximately
40–50 Gy in 20–25# over 4 to 5 weeks. Accelerated,
hyper and hypo-fractionated regimens remain
investigational.
Recommendations
• The most common management approach is
surgery followed by post-operative radiation
therapy ideally within six weeks (R)
• Radiation is given first if a response to
radiation may lead to organ preservation (G)
• Radiotherapy should be delivered within an
accredited department using megavoltage
photons from a linear accelerator (typical
energies 4–6 MV) as an unbroken course (R)
• Intensity modulated radiotherapy is the
standard of care as it can improve target
coverage, allow for dose escalation and
facilitate organ sparing to reduce toxicity (R)
Chemotherapy. Consensus statements are difficult due
to the lack of adequately powered, randomised evi-
dence. This is given either as a short course induction
and/or neoadjuvant regime pre-RT or surgery for
rapid symptom control, and/or concurrently as a radi-
ation sensitiser.
The neoadjuvant approach is not associated with
improved overall outcomes, but is a practical solution
to pre RT tumour shrinkage, as modern RT delivery
relies on a static patient contour, to deliver dose accur-
ately and safely.19 This is usually cisplatin-based and in
the phase II setting produces a response in about two-
thirds of patients.
Concurrent use of chemotherapy with RT is asso-
ciated with a small, but measurable improvement in
survival for SCCs of the head and neck in general,
with improved disease-free and overall survival at
five years to approximately 70 and 67 per cent, respect-
ively suggested. For the rarer tumour types of the sinus
area, there is no strong randomised evidence currently
to support its use routinely.
NOSE AND PARANASAL SINUS TUMOURS: UK GUIDELINES
Small-scale observational studies have reported on
topical and intra-arterial chemotherapy, but are not
recommended.
Chemotherapy has also been reported to be of use in
undifferentiated carcinomas, neuroendocrine and small
cell carcinomas. Excellent local and distant control
rates for olfactory neuroblastoma have been demon-
strated with local therapy alone and chemotherapy in
this setting is experimental, but often given in the pres-
ence of locally advanced disease. For sinonasal SCC,
there is no randomised evidence in favour of the use
of concomitant chemoradiation. Evidence supporting
its use both in the primary and adjuvant setting can
be extrapolated from other head and neck
malignancies.
Chemotherapy may improve quality of life and offer
a modest survival benefit in the palliative setting, trans-
lating from benefit seen in other head and neck SCC
sites.20 Molecular targeted treatments are under inves-
tigation, but none have proven benefit to date.
The role of chemotherapy in paranasal sinus malig-
nancy is limited to the following settings: as part of
triple therapy, e.g. embryonal rhabdomyosarcoma, con-
currently with radiation in locally advanced disease,
e.g. SCC of maxilla, for disseminated lymphoprolifera-
tive malignancy and for palliation, e.g. poorly differen-
tiated SCC with disseminated disease.
Palliation. Some patients present with advanced disease
where radical treatment is not appropriate. Surgery, RT
and chemotherapy all have a potential role in palliation.
Palliative RT treatment requires high doses to
achieve any significant tumour control, and short frac-
tionation regimes are associated with marked acute tox-
icity. Regimens that can be considered on an individual
basis include 55 Gy in 20# over four weeks, 27 Gy in
6# over three weeks and 36 Gy in 12# over two-and-
a-half weeks. If the patient has a localised disease
FIG. 3
Follow-up algorithm for malignant sinonasal tumours.7
S117
recurrence, then retreatment with IMRT or stereotactic
RT may be considered especially if there has been a
long disease-free interval.
Follow-up. Follow-up is needed for detection of recur-
rence and to manage surgical sequelae (nasal crusting,
epiphora, etc.). Follow-up should be lifelong as some
tumours can recur many years after treatment and
should include careful examination of the cavity with
the endoscope and MRI scans. Imaging should
include the neck in olfactory neuroblastoma (see
below). (Figure 3)
Key points
• Endoscopy and imaging (computed tomography
and magnetic resonance imaging) are key to asses-
sing tumour extent and planning surgical approach
• Endoscopic techniques enable low morbidity and
low recurrence rates to be achieved in suitable
tumours and may be performed for curative or pal-
liative reasons
• A high level of expertise in endoscopic sinus
surgery and skull base and/or dural reconstruction
is a necessity before undertaking endoscopic
resections
• Neurosurgical support and neuronavigation
should be routinely available in centres undertak-
ing this surgery
• Reconstruction and rehabilitation needs should be
integrated into the treatment plan for patients
undergoing open surgery
• The majority of patients will require adjuvant
radiotherapy
• Diligent tumour surveillance with nasal endos-
copy and interval magnetic resonance imaging
scans is a necessity following treatment of sinona-
sal malignancy.
References
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et al. Sinonasal inverted papilloma: 84 patients treated by endos-
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Maroldi R et al. Endoscopic surgery for juvenile angiofibroma:
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et al. Craniofacial resection for malignant paranasal sinus
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2008;97:658–64
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Beham A et al. European position paper on endoscopic manage-
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2010;22:1–144
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cial resection for malignant tumors of the anterior skull base.
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neuroblastoma – a 35 year experience and suggested follow-
up protocol, Laryngoscope 2014;124:1542–49
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oma: a review of 115 cases assessing outcomes of surgery, post-
operative radiotherapy and endoscopic resection. Rhinology
2012;50:203–10
15 Zanation A, Ferlito A, Rinaldo A, Gore M, Lund V, Mckinney K
et al. When, how and why to treat the neck in patients with esthe-
sioneuroblastoma: a review. Eur Arch ORL 2010;267:1667–71
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Indications and Techniques, 3rd edn. Lippincott, 2006
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Intensity-modulated radiotherapy for sinonasal cancer:
improved outcome compared to conventional radiotherapy. Int
J Radiat Oncol Biol Phys 2010;78:998–1004
18 Bristol IJ, Ahamad A, Garden AS, Morrison WH, Hanna EY,
Papadimitrakopoulou VA et al. Postoperative radiotherapy for
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treatment. Int J Radiat Oncol Biol Phys 2007;68:719–30
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Roux FX. Cisplatin-based neoadjuvant chemotherapy and com-
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Address for correspondence:
V J Lund,
Royal National Throat Nose and Ear Hospital, Royal Free
Hampstead NHS Trust,
London, UK
E-mail: v.lund@ucl.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S119–S124. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000542

Management of lateral skull base cancer: United

Kingdom National Multidisciplinary Guidelines

JJ HOMER1, T LESSER2, D MOFFAT3, N SLEVIN4, R PRICE5, T BLACKBURN6

1
Manchester Academic Health Sciences Centre, University of Manchester, Manchester, 2Department of ENT/Head
and Neck Surgery, University Hospital Aintree, Liverpool, 3Department of Neuro-otology and Skull Base Surgery,
University of Cambridge, Cambridge University Teaching Hospitals NHS Foundation Trust, Cambridge,
4
Department of Clinical Oncology, Christie Hospital NHS Trust, Manchester, 5Department of Plastic and
Reconstructive Surgery, Cambridge University Teaching Hospitals NHS Foundation Trust, Cambridge, and
6
Department of Oral and Maxillofacial Surgery, Manchester Royal Infirmary, Manchester, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. It provides recommendations on the work up and management of lateral skull base cancer
based on the existing evidence base for this rare condition.

Recommendations
• All patients with more than one of: chronic otalgia, bloody otorrhoea, bleeding, mass, facial swelling or palsy
should be biopsied. (R)
• Magnetic resonance and computed tomography imaging should be performed. (R)
• Patients should undergo audiological assessment. (R)
• Carotid angiography is recommended in select patients. (G)
• The modified Pittsburg T-staging system is recommended. (G)
• The minimum operation for cancer involving the temporal bone is a lateral temporal bone resection. (R)
• Facial nerve rehabilitation should be initiated at primary surgery. (G)
• Anterolateral thigh free flap is the workhorse flap for lateral skull base defect reconstruction. (G)
• For patients undergoing surgery for squamous cell carcinoma, at least a superficial parotidectomy and selective
neck dissection should be carried out. (R)

Introduction long history of chronic middle or external ear infection,

Primary cancers of the temporal bone (TB) and lateral
skull base are comparatively rare, accounting for 0.2
per cent of all head and neck cancers. They consist of
different sites of cancer with a range of pathologies.
Consequently, there is little evidence as to best practice.
Over ten times more frequent are cancers of the skin
and parotid invading the TB. Despite this there is
even less evidence of best practice. Lateral skull base
cancer can be considered to comprise any of the entities
described in Table I.
Clinical presentation
Late diagnosis of patients with cancers of the external
auditory meatus (EAM) and middle ear (ME) is not
uncommon and this should be considered in any
patients with: chronic otalgia, bloody otorrhoea, bleed-
ing, mass, facial swelling or palsy.1 Clinical findings of
excoriation, ulceration and granulation tissue should be
considered as suspicious. Some patients may have a
which can be a pre-disposing factor.
Skin cancers present as visible or itchy skin and/or
pinna lesions. Tumours of the infratemporal fossa
may present with a subtle mass or fullness immediately
above the zygoma or with pain (which can be easily
misdiagnosed as temporal mandibular joint pain).
Assessment and staging
Clinical examination
Confirmation of diagnosis is mandatory before treat-
ment and is gained by biopsy of the pinna, skin,
EAM or ME. Advanced parotid cancers should be
diagnosed through cytopathology or, occasionally if
necessary, incision biopsy. Tumours of the infratem-
poral fossa often will require a surgical biopsy via
access superior or inferior to the zygoma as necessary.
Cytology is possible, but, as many tumours here are
sarcomas, histopathology is required. The differential
S120 JJ HOMER, T LESSER, D MOFFAT et al.

TABLE I Carotid angiography and balloon occlusion are occa-

ENTITIES THAT COME UNDER THE CATEGORY OF sionally required to assess ipsilateral carotid artery
LATERAL SKULL BASE CANCER involvement. If a tumour is thought unresectable
Site Main pathologies without internal carotid artery sacrifice, then a tempor-
ary balloon occlusion test can be performed. If success-
Advanced skin cancer SCC ful, permanent pre-operative occlusion via coils can be
(conchal bowl/pinna/peri- BCC
auricular skin) Melanoma performed (ideally two weeks pre-operatively).
Advanced parotid cancers Salivary gland malignant
(involving ear/temporal neoplasms (generally high Audiology
bone) grade), including metastatic
skin SCC to intra-parotid Pure tone audiogram of both ears should be performed
lymph nodes pre-operatively.
Infratemporal fossa temporo- Sarcomas (e.g.
mandibular joint chondrosarcomas,
rhabdosarcoma, Pre-treatment staging
osteosarcoma)
EAM/ME Most SCC (80%) There is no Union for International Cancer Control
BCC (UICC) or American Joint Committee on Cancer
Skin adnexal cancers (AJCC) staging system for cancers of the TB or
lateral skull base. However, many use the revised
Pittsburgh staging system (Table II). The standard
diagnosis is myriad, but care must be taken to exclude UICC staging is used for neck and distant metastases.
pseudotumoral skull base osteomyelitis of the TB (also
called necrotising otitis externa) and inflammatory dis- Recommendations
eases such as granulomatosis with polyangiitis.
• All patients with more than one of: chronic
otalgia, bloody otorrhoea, bleeding, mass,
Imaging considerations
facial swelling or palsy should be biopsied (R)
In most cases, both computed tomography (CT) and
• Magnetic resonance and CT imaging should
magnetic resonance imaging (MRI) should be used.
be performed (R)
Computed tomography (fine cut, high resolution) is
essential for external auditory canal (EAC) erosion, • Patients should undergo audiological
extent of middle ear and mastoid involvement, spread assessment (R)
into jugular bulb, carotid canal, tegmen, temporoman- • Carotid angiography is recommended in
dibular joint (TMJ), parotid and beyond. It can also select patients (G)
stage the neck. Magnetic resonance differentiates • The modified Pittsburg T-staging system is
mucosal swelling or mastoid fluid from tumour; is recommended (G)
superior at ascertaining dural or brain involvement;
and gives more detail of parapharyngeal space and
infratemporal fossa involvement.
Despite high-resolution scanning using both modal- Treatment planning and prognosis
ities, both over and under estimation of the extent of the There should be a specific multidisciplinary team (MDT)
tumour occurs. Patients should be prepared for more dealing with skull base cancers. For sarcomas, there
extensive surgery or abandoning surgery if the scans should be liaison with the sarcoma MDT, and, for paedi-
prove wrong. atric sarcomas, with the paediatric oncology MDT.
Depending on the pathology of the tumour, imaging Most patients with operable cancer of the lateral
of the thorax (squamous cell carcinoma (SCC)) or skull base are treated with primary surgery, with the
whole body may be required (sarcomas, melanoma). exception of some sarcomas. Given the low incidence
of lateral skull base cancer, the variety of precise
sites of origin, heterogeneity of tumour pathology and
TABLE II individual circumstance, it is difficult to generalise
MODIFIED PITTSBURG STAGING SYSTEM2 treatment guidelines. The commonest scenarios are of
SCC arising in the ear or TB (ME and/or EAM) and
T1 Tumour limited to the EAC without bony erosion or
evidence of soft tissue extension advanced parotid cancers. The situation of advanced
T2 Tumour with limited EAC erosion (not full thickness) or cutaneous SCC invading the TB is not materially
radiological findings consistent with limited (<0.5 cm) different.3
soft tissue involvement
T3 Tumour eroding the osseous EAC (full thickness) with
limited (<0.5 cm) soft tissue involvement of middle ear Cancers arising in the temporal bone
and/or mastoid or causing facial paralysis at presentation
T4 Tumour eroding the cochlear, petrous apex, medial wall of General principles
middle ear, carotid canal, jugular foramen, or dura or with
extensive (>0.5 cm) soft tissue involvement For cancer arising in the TB, the most favourable sur-
vival rates are achieved with an en bloc extended TB
LATERAL SKULL BASE CANCER: UK GUIDELINES
resection and post-operative radiotherapy (RT).4–6 The
influence of ME involvement on prognosis is critical.
T1 and T2 lesions lateral to the tympanic membrane
have cure rates near to 100 per cent with true enbloc
resections without breach of the tumour. The majority
of T3 tumours are also cured with disease specific sur-
vival rates over 70 per cent, whereas T4 five-year sur-
vival results vary between 30 and 50 per cent.1,7,8
Nodal metastasis has a major influence on prognosis.5,9
Equally critical for prognosis is a histologically-proven
complete microscopic resection.4,8
Extension superiorly through the tegmen leads to
dural and cerebral involvement. Dural involvement is
an adverse prognostic indicator, but around one-third
of such patients are curable with the appropriate
surgery.5 Cerebral involvement rarely confers any
chance of cure.
On the other hand, T4 tumours that are T4 by virtue of
anterior invasion to the TMJ and/or pre-auricular tissue
have a much better prognosis than other T4 tumours.9
Resection of the intra-petrous carotid is possible.
Some patients can benefit from pre-operative radio-
logical permanent occlusion of the carotid artery,
subject to successful balloon occlusion. However, the
cancer-mortality in this group of patients with petrous
apex involvement is high, due to difficulties achieving
full microscopic resection around this area, and the
post-operative morbidity is high due to, amongst
other things, multiple cranial nerve deficits from a
resection of this extent.
Thus, for patients with a combination of high mor-
bidity with low chance of surgical cure, consideration
should be given not to offer primary surgery.5
Temporal bone surgery
Lateral temporal bone resection (LTBR) should be
regarded as the minimum oncological operation for T1
and T2 lesions5,10. Essential elements of LTBR are (1)
excision lateral to facial nerve; (2) conchal bowl resec-
tion; and (3) bony cuts: mastoid to middle fossa dura
(or leaving a thin layer of bone), anteriorly into zygo-
matic aircells and TMJ, inferiorly to stylomastoid
foramen, hypotympanum to TMJ.
Additional options include (see below): resection of
entire pinna and periauricular skin; condyle/mandible,
parotid, extension of resection into parapharyngeal
space and infratemporal fossa, neck dissection, facial
nerve sacrifice and cable graft.
Extended temporal bone resection (ETBR) is required
for more extensive tumours involving the middle ear11.
The essential elements of EBTR are (1) facial nerve
sacrifice; (2) posterior and middle craniotomy; (3) laby-
rinthectomy; (4) transection of internal auditory canal;
(5) resection of petrous tip; (6) exposure of intra-petrous
portion of the carotid; and (7) total parotidectomy.
Additional options include: craniectomy (squamous
TB; sphenoid wing, posterior fossa); mandibulectomy;
parapharyngeal and/or infratemporal fossa resection;
S121
extension to jugular foramen; lower cranial nerve sacri-
fice; internal carotid artery; dura; brain.
Recommendation
• The minimum operation for cancer involving
the temporal bone is a lateral temporal bone
resection (R)
Resection of other structures in TB surgery
Parotid gland. When performing TB resections for TB
cancers and advanced skin cancers, the parotid gland
may be either involved directly by tumour or be har-
bouring intra-parotid lymph node metastases (it may
contain the primary echelon lymph node). The former
may be suggested by pre-operative scans. Therefore,
for all resections, at least a superficial parotidectomy
should be carried out.10 For advanced T3/T4 TB
SCCs, total parotidectomy should be carried out,
which also facilitates access to the parapharyngeal
space, infratemporal fossa and masticator space. For
basal cell carcinoma (BCC) without evidence of
direct invasion into or near the parotid gland, paroti-
dectomy can be omitted.
Temporo-mandibular joint/mandible. The standard
anterior bony cut in a lateral TB resection goes into
the TMJ. There is therefore some degree of disruption
of TMJ function as a consequence. If there is involve-
ment of or near the TMJ/condyle, it is recommended
that a partial mandibulectomy is carried out, which
may range from condylectomy to resection from man-
dibular notch to angle. If the latter is done, the inferior
alveolar nerve should be preserved, if oncologically
sound to do so. There is, however, no need for
routine resection to include the TMJ in lateral temporal
bone resection (LTBR).5
Temporal bone resection in parotid cancers
Almost all parotid cancers abutting the TB are easier to
remove if an inferior TB resection is done to get medial
and posterior to the tumour rather than finding the
facial nerve outside the stylomastoid foramen and
getting too close to the tumour. This improvement in
surgical access both improves prognosis and ease of
facial nerve grafting if required.12,13 For parotid
tumours with EAM or TB involvement, at least a
lateral TB resection will be required.
Facial nerve
Facial nerve involvement by tumour is a significant
adverse prognostic factor. Pre-operative facial nerve
dysfunction due to facial nerve involvement by
tumour requires sacrifice of the nerve as part of the
resection required. For some patients with normal func-
tion pre-operatively, it may be technically impossible to
resect a tumour without nerve sacrifice if the nerve is
totally encased by tumour, bearing in mind the aim
S122
of surgery is complete, preferably monobloc, tumour
resection with margins. When the facial nerve is sacri-
ficed, the proximal stump at the limit of the sacrifice
should be sent for frozen section pathology.
In cases in which nerve sacrifice is necessary, one or
more of the following steps should be considered
detailed below. It should be borne in mind that the
best time to perform many of these interventions is at
the time of tumour resection, as virtually every
patient in this group will go on to have post-operative
RT.
A cable graft from ME facial nerve to intra-parotid
branches can be performed if (a) there is enough
proven tumour-free proximal facial nerve (otherwise a
facial-hypoglossal anastamosis can be considered)
and (b) if the peripheral branches can be identified
(this may be difficult when a radical en-bloc parotidect-
omy with overlying skin is performed). Useful donor
nerves include greater auricular nerve, sural nerve or
lateral cutaneous nerve of thigh (easily available if har-
vesting an anterolateral thigh free flap). If an alternative
lengthening of telomeres (ALT) free flap is to be
employed, this can be used as a chimaeric flap, with
separate components for volume restoration and facial
function and vascularised interposition nerve grafting.
Otherwise, either static procedures can be employed
such as fascia lata sling for oral commissure/cheek sus-
pension or dynamic procedures such as lengthened
temporalis myoplasty (e.g. Labbé type I or II), if the
deep temporal nerve and artery are preserved.
Oculoplastic interventions (e.g. gold weight, cantho-
plasty) can be performed at the time of tumour resec-
tion or later on.
Recommendation
• Facial nerve rehabilitation should be initiated
at primary surgery (G)
Reconstruction
The aims of reconstruction of lateral skull base defects
can be considered hierarchically:
• Protection for the brain when the dura mater is
breached.
• Skin defect.
• Auricular defect.
• Tissue volume defect and mandible defect.
• Functional defect-facial nerve.
Dural defects are normally repaired with non-vascu-
larised tissue such as autologous fascia lata grafts, peri-
cardial xenografts or synthetic materials.
Reconstruction of the skin defect should be consid-
ered with the volume defect, this being determined
JJ HOMER, T LESSER, D MOFFAT et al.
by extent of temporal bone resection, parotidectomy
and mandibulectomy in particular.14
For smaller skin defects without much volume loss,
options include radial forearm free flap, cervicofacial
rotation flap, temporalis flap and supraclavicular
artery island flap. These can be used to reconstruct
small skin/auricle defects with modest volume loss.
For most defects after temporal bone resection, the
anterolateral thigh free flap offers optimal reconstruc-
tion, offering bulk (variable by the inclusion of
vastus lateralis), and enough skin for most defects
(which can be reduced by de-epithelialisation if the
auricle is not resected).14 It is reliable, has the requisite
tissue and minimal donor site morbidity. It allows vas-
cularised fascia lata to be used for static facial resuspen-
sion or the lateral cutaneous femoral nerve for either
sensory innervation of the flap or an interpositional
facial nerve graft. Also, the accessible donor site
allows for concomitant flap harvest and tumour abla-
tion. Alternative flaps include latissimus dorsi, rectus
abdominis or deep inferior epigastric artery perforator,
radial forearm, medial sural artery and lateral arm flaps.
In a vessel-depleted neck or in a patient unsuitable
for microvascular surgery, lower trapezius muscle
island flap (if the transverse cervical vessels are
intact) or superior trapezius flap (when a radical neck
dissection has been performed) can be used. The use
of pectoralis major or delto-pectoral flap is sub-
optimal as the lateral skull base is at or beyond the
limits of rotation in many cases.
It is feasible to leave selected condylar resections
unreconstructed accepting minor dental occlusal dis-
turbance. Where mandibular reconstruction is required,
a composite microvascular flap such as a chimeric thor-
acodorsal artery perforator – scapular osteomusculocu-
taneous flap can restore a large mandibular and lateral
skull defect.
Recommendation
• Anterolateral thigh free flap is the workhorse
flap for lateral skull base defect
reconstruction (G)
Neck dissection
Up to 20 per cent of patients with temporal bone SCC
will have lymph node metastases. The need for neck
dissection depends on the pathology. As for any head
and neck cancer, clinically or radiologically staged
N + necks require comprehensive neck dissection,
but level 1a (submental) can be spared. In the setting
of N0 neck, it is also recommended that neck dissection
(levels 1b, 2–5) is performed for all temporal bone
SCC.15 The same applies to advanced parotid carcin-
omas with temporal bone involvement.
LATERAL SKULL BASE CANCER: UK GUIDELINES
Recommendation
• For patients undergoing surgery for
squamous cell carcinoma, at least a superficial
parotidectomy and selective neck dissection
should be carried out (R)
Radiation therapy
Post-operative RT
Most T2–T4 SCCs will require post-operative RT,5 as
will advanced parotid cancers requiring temporal bone
surgery. T1 and selected T2 SCCs without adverse
histological features (particularly peri-neural infiltra-
tion) and with proven clear margins may not require
adjuvant therapy. Dosimetry with electrons is unpre-
dictable due to tissue heterogeneity and photon
therapy is preferred using three-dimensional conformal
or intensity modulated techniques (IMRT). The clinical
target volume is determined from pre-operative
imaging and further informed from MDT feedback
on operative and histopathological findings.
Conformal RT is computer planned and the target
volume often resembles a transaxial triangular shape
with the base laterally. A simple pair of horizontal
wedged lateral oblique fields may suffice, with beams
exiting on either side of the contralateral parotid. An
additional lateral field with vertical wedging may
improve homogeneity longitudinally.
Intensity modulated techniques may well reduce
dose to the ipsilateral cochlea (if this is separate from
the tumour volume) and oral cavity. Chronic otomas-
toiditis and TB necrosis following RT can be reduced
by restricting the volume of bone treated to high dose
as far as possible. The contralateral parotid, bilateral
submandibular glands, oral cavity, mandible, cochlea
as well as central nervous system (CNS) structures
should be routinely contoured and given constraint
doses.
Post-operative doses used for head and neck cancer
are 60 Gy in 30 fractions for moderate risk and 66 Gy
in 33 fractions for high risk; these doses can potentially
be applied for lateral skull base cancers, but the normal
tissue (particularly CNS) complication rate is clinically
significant at doses above 60 Gy. Synchronous post-
operative treatment with cisplatin can be also
considered.16
Primary RT
When primary surgery is not considered possible, or
too morbid, definitive RT may be used, with overall
cure rates of just under half of patients overall.16
Clinical target volume is based on staging imaging,
preferably with both CT and MR imaging (MRI).
Higher biological doses are used compared with the
post-operative setting so that optimal conformality is
essential to reduce treatment complications. Standard
S123
IMRT doses can be used: 66 Gy in 30 fractions for
macroscopic disease, 60 Gy for high risk microscopic
areas and 54 Gy for moderate risk microscopic areas;
these doses may be modified according to the volume
of CNS tissue in the clinical target volume. In view
of the emphasis on conformality, there may well be a
role for proton beam therapy in some cases.
Synchronous treatment with cisplatin can be consid-
ered; an alternative strategy is to use cetuximab.
Other lateral skull base cancer operations
Tumours of the infratemporal fossa are more rare and
heterogeneous and thus need an individualised opera-
tive approach. Examples include facial translocation,
sub-temporal pre-auricular, orbito-zygomatic and
trans-TB (Fisch) approaches.17–20
Post-operative care issues
In addition to VII nerve issues, all lower cranial nerves
essential for swallowing and voice (IX, X, XII) are at
risk of injury or sacrifice in surgery for advanced
tumours. Care of the patient in this situation must
include close involvement of speech and language
therapy. Interventions include either pre- or post-
operative percutaneous gastrostomy; naso-gastric
tube; tracheostomy if aspirating on saliva. Later inter-
ventions include vocal cord medialisation and crico-
pharyngeal myotomy.
Ipsilateral total or total conductive hearing deficit is
an inevitable outcome of TB resection. Pre-operative
audiological assessment of the contralateral ear will
identify patients with a pre-existing deficit. This may
be corrected or improved with appropriate aiding in
either the pre- or post-operative period. Total conduct-
ive hearing loss can be rehabilitated through an osseo-
integrated bone anchored hearing aid (BAHA). Total
hearing loss can be rehabilitated through either a
BAHA or a bilateral contralateral routing of signals
(BI-CROS) aid.
Post-operative vertigo is expected if there is resection
of a functioning labyrinth. If vestibular compensation is
protracted and incomplete, referral for vestibular
rehabilitation services should be considered.
Palliative care
The local issues that affect patients when tumours are
inoperable or recur are generally pain (particularly
through dural involvement) and fungation. Therefore,
the instigation of a comprehensive analgesic regimen
is required. Fungation can be a particular problem,
made worse by the prominent site of the cancer.
Radiotherapy can be given for palliative intent, if not
already given, and can be useful for both pain and fun-
gation. Short fractionation schedules may well be
appropriate in these situations using, for example,
30 Gy in 10 fractions and a single lateral megavoltage
photon field. If RT has previously been given and there
is a reasonable interval (more than 12 months), then re-
irradiation is sometimes beneficial.
S124
Key points
• Cancer of the lateral skull base is rare and constitutes
a heterogeneous group of cancers and sites of origin
• Most cancers are treated with primary surgery and
post-operative radiotherapy
• For temporal bone cancers, the boundary of the tym-
panic membrane is paramount in prognosis. Most T1
and 2, and many T3 cancers are cured
• The minimum operation for a temporal bone cancer
should be a lateral temporal bone resection
• Lateral temporal bone resection should be consid-
ered in advanced parotid cancers
• Achieving clear microscopic margins at surgery is
critical
• Salvage surgery is often not successful: the best, and
usually only, chance of cure is at initial surgery
• For patients with advanced cancers, particularly at
the petrous apex or with dural or facial nerve
involvement, cure rates drop considerably
• For patients with advanced cancers undergoing
surgery, there are many rehabilitation issues
• The anterolateral thigh free flap is the workhorse for
reconstruction.
References
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the temporal bone: outcomes of radical surgery and post-
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2 Moody SA, Hirsch BE, Myers EN. Squamous cell carcinoma of
the external auditory canal: an evaluation of a staging system.
Am J Otol 2000;21:582–88
3 Essig GF, Kitipornchai L, Adams F, Zarate D, Gandhi M,
Porceddu S et al. Lateral temporal bone resection in advanced
cutaneous squamous cell carcinoma: report of 35 patients.
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4 Bacciu A, Clemente IA, Piccirillo E, Ferrari S, Sanna M.
Guidelines for treating temporal bone carcinoma based on
long-term outcomes. Otol Neurotol 2013;34:898–907
5 Masterson L, Rouhani M, Donnelly NP, Tysome JR, Patel P,
Jefferies SJ et al. Squamous cell carcinoma of the temporal
bone: clinical outcomes from radical surgery and postoperative
radiotherapy. Otol Neurotol 2014;35:501–8
6 Madsen AR, Gundgaard MG, Hoff CM, Maare C, Holmboe P,
Knap M et al. Cancer of the external auditory canal and middle
ear in Denmark from 1992 to 2001. Head Neck 2008;30:1332–8
7 Lassig AA, Spector ME, Soliman S, El-Kashlan HK. Squamous
cell carcinoma involving the temporal bone: lateral temporal
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Yin M, Ishikawa K, Honda K et al. Analysis of 95 cases of squa-
mous cell carcinoma of the external and middle ear. Auris Nasus
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9 Mazzoni A, Danesi G, Zanoletti E. Primary squamous cell car-
cinoma of the external auditory canal: surgical treatment and
long-term outcomes. Acta Otorhinolaryngol Ital 2014;34:
129–37
10 Zhang T, Li W, Dai C, Chi F, Wang S, Wang Z. Evidence-based
surgical management of T1 or T2 temporal bone malignancies.
Laryngoscope 2013;123:244–8
11 Chang CH, Shu MT, Lee JC, Leu YS, Chen YC, Lee KS.
Treatments and outcomes of malignant tumors of external audi-
tory canal. Am J Otolaryngol 2009;30:44–8
12 Mehra S, Morris LG, Shah J, Bilsky M, Selesnick S, Kraus DH.
Outcomes of temporal bone resection for locally advanced
parotid cancer. Skull Base 2011;21:389–96
13 Shao A, Wong DK, McIvor NP, Mylnarek AM, Chaplin JM,
Izzard ME et al. Parotid metastatic disease from cutaneous squa-
mous cell carcinoma: prognostic role of facial nerve sacrifice,
lateral temporal bone resection, immune status and P-stage.
Head Neck 2014;36:545–50
14 Hanasono MM, Silva AK, Yu P, Skoracki RJ, Sturgis EM,
Gidley PW. Comprehensive management of temporal bone
defects after oncologic resection. Laryngoscope 2012;122:
2663–9
15 Rinaldo A, Ferlito A, Suarez C, Kowalski LP. Nodal disease in
temporal bone squamous carcinoma. Acta Otolaryngol 2005;
125:5–8
16 Takenaka Y, Cho H, Nakahara S, Yamamoto Y, Yasui T,
Inohara H. Chemoradiation therapy for squamous cell carcin-
oma of the external auditory canal: a meta-analysis. Head
Neck 2015;37:1073–80
17 Sekhar LN, Schramm VL Jr, Jones NF. Subtemporal-preauricu-
lar infratemporal fossa approach to large lateral and posterior
cranial base neoplasms. J Neurosurg 1987;67:488–99
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sembly in the management of skull-base tumors. Otolaryngol
Clin North Am 1991;24:1465–97
19 Suarez C, Llorente JL, Munoz C, Garcia LA, Rodrigo JP. Facial
translocation approach in the management of central skull base
and infratemporal tumors. Laryngoscope 2004;114:1047–51
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JM. Preauricular transmandibular and transzygomatic approach
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Address for correspondence:
JJ Homer,
Manchester Academic Health Sciences Centre,
University of Manchester,
Manchester, UK
E-mail: Jarrod.J.Homer@manchester.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S125–S132. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000554

Non-melanoma skin cancer: United Kingdom

National Multidisciplinary Guidelines

C NEWLANDS1, R CURRIE2, A MEMON3, S WHITAKER4, T WOOLFORD5

1
Department of Oral and Maxillofacial Surgery, Royal Surrey County Hospital, Guildford, 2Department of
Oral and Maxillofacial Surgery, Ayrshire and Arran Health Board, 3Department of Dermatology, Southport
and Ormskirk NHS Trust, Ormskirk, 4Department of Oncology, Royal Surrey County Hospital, Guildford,
and 5Department of Otolaryngology-Head and Neck Surgery, Manchester Royal Infirmary, Oxford Road,
Manchester, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. This paper provides consensus recommendations on the management of cutaneous basal cell
carcinoma and squamous cell carcinoma in the head and neck region on the basis of current evidence.

Recommendations
• Royal College of Pathologists minimum datasets for NMSC should be adhered to in order to improve patient
care and help work-force planning in pathology departments. (G)
• Tumour depth is of critical importance in identifying high-risk cutaneous squamous cell carcinoma (cSCC),
and should be reported in all cases. (R)
• Appropriate imaging to determine the extent of primary NMSC is indicated when peri-neural involvement or
bony invasion is suspected. (R)
• In the clinically N0 neck, radiological imaging is not beneficial, and a policy of watchful waiting and patient
education can be adopted. (R)
• Patients with high-risk NMSC should be treated by members of a skin cancer multidisciplinary team (MDT) in
secondary care. (G)
• Non-infiltrative basal cell carcinoma (BCC) <2 cm in size should be excised with a margin of 4–5 mm.
Smaller margins (2–3 mm) may be taken in sites where reconstructive options are limited, when
reconstruction should be delayed. (R)
• Where there is a high risk of recurrence, delayed reconstruction or Mohs micrographic surgery should be used.
(R)
• Surgical excision of low-risk cSCC with a margin of 4 mm or greater is the treatment of choice. (R)
• High-risk cSCC should be excised with a margin of 6 mm or greater. (R).
• Mohs micrographic surgery has a role in some high-risk cSCC cases following MDT discussion. (R)
• Delayed reconstruction should be used in high-risk cSCC. (G)
• Intra-operative conventional frozen section in cSCC is not recommended. (G)
• Radiotherapy (RT) is an effective therapy for primary BCC and cSCC. (R)
• Re-excision should be carried out for incompletely excised high-risk BCC or where there is deep margin
involvement. (R)
• Incompletely excised high-risk cSCC should be re-excised. (R)
• Further surgery should involve confirmed marginal clearance before reconstruction. (R)
• P+ N0 disease: Resection should include involved parotid tissue, combined with levels I–III neck dissection, to
include the external jugular node. (R)
• P+ N+ disease: Resection should include level V if that level is clinically or radiologically involved. (R)
• Adjuvant RT should include level V if not dissected. (R)
• P0 N+ disease: Anterior neck disease should be managed with levels I–IV neck dissection to include the
external jugular node. (R)
• P0 N+ posterior echelon nodal disease (i.e. occipital or post-auricular) should undergo dissection of levels
II–V, with sparing of level I. (R)
• Consider treatment of the ipsilateral parotid if the primary site is the anterior scalp, temple or forehead. (R)
• All patients should receive education in self-examination and skin cancer prevention measures. (G)
• Patients who have had a single completely excised BCC or low-risk cSCC can be discharged after a single post-
operative visit. (G)
S126
• Patients with an excised high-risk cSCC should be reviewed three to six monthly for two years, with further
annual review depending upon clinical risk. (G)
• Those with recurrent or multiple BCCs should be offered annual review. (G)
Introduction
The incidence of all types of skin cancer is increasing.
The non-melanoma skin cancers (NMSCs) are mostly
basal cell carcinoma (BCC), the commonest human
cancer in Caucasians, and cutaneous squamous cell car-
cinoma (cSCC). Over 80 per cent of these tumours occur
on the skin of the head and neck. Most NMSC is easily
curable. Death is rare; when it occurs, it does so from
metastatic cSCC, or from local invasion by neglected
BCC or cSCC. The majority of research regarding the
management of skin cancer relates to populations of
Caucasians in Australia and North America, and differ-
ent patterns of disease are likely to exist in Europe and
the UK. There are no large prospective randomised, con-
trolled trials in which different treatments of NMSC
have been compared. Organisation of skin cancer ser-
vices including the treatment of NMSC within the UK
National Health Service is determined by National
Institute for Health and Care Excellence (NICE) guid-
ance.1 This section discusses the management of
NMSC, confined to BCC and cSCC of the head and
neck. It briefly outlines the management of the
primary lesion, and discusses the investigation and treat-
ment of regional metastatic cSCC. Squamous cell car-
cinoma of the lip is dealt with elsewhere in the
guidelines. The reader is advised to access current
guidelines referenced in this document for further infor-
mation on the management of NMSC.2–6
Epidemiology and aetiology
The incidence of NMCS is underreported in the UK
due to inconsistent data collection. The incidence is
known to be rising and is estimated to do so until
2040. Non-melanoma skin cancer is more common in
men, and with increasing age. The age shift in the
population has resulted in an overall increase in total
number of skin cancers.
The major predisposing factor for the development
of NMSC is chronic sunshine exposure, particularly
in childhood. Other common factors include fair skin,
other forms of ionising radiation, immunosuppression,
previous skin malignancy and premalignant states, such
as multiple actinic keratoses.
Immunosuppressed patients with skin cancers com-
prise mainly transplant patients and those with chronic
haematological malignancies. These patients frequently
develop multiple skin cancers, which are often aggres-
sive in nature. Skin cancers comprise 40–50 per cent
of post-transplant malignancies. There is an increased
risk of skin cancer in patients who are taking anti-
tumour necrosis factor drugs. Genetic conditions and
exposure to sensitising chemicals are rare causes of
NMSC as is the occurrence of cSCC in chronic wounds.
C NEWLANDS, R CURRIE, A MEMON et al.
Presentation and diagnosis of NMSC
Basal cell carcinoma
Nodular lesions are the most common form of BCC.
Morphoeic BCCs are found almost exclusively on the
head and neck, the commonest single site being the
nose. Superficial BCCs are predominantly found on
the trunk. Nodular BCC may have clinical cystic or pig-
mented variants. Basal cell carcinoma has a number of
well-described histological subtypes.7
The 2014 Royal College of Pathology7 dataset
adopts the term ‘infiltrative BCC’ for all high-risk
histological variants and notes that many BCCs
contain both high- and low-risk subtypes (Table 1).
Cutaneous squamous cell carcinoma
Cutaneous squamous cell carcinoma typically presents
as an indurated nodular keratinising or crusted tumour
that may ulcerate, or it may present as an ulcer
without evidence of keratinisation. Cutaneous squa-
mous cell carcinoma of the nasal vestibule or of the
ear canal is often diagnosed late, with resulting poor
prognosis, as it can be misdiagnosed as other
common conditions.
Diagnosis
Diagnosis of NMSC is usually clinical, with subsequent
histological confirmation following excision. The
‘stretch test’ has been shown to improve diagnostic
accuracy in BCC. Dermoscopy improves initial diagnos-
tic rate in all NMSC and may be of some assistance in
determining a BCC sub-type. Pre-excisional tissue diag-
nosis can be indicated particularly if a graft or flap will
be required for reconstruction, or in an anatomically
complex area such as the nose. In most circumstances,
this is best achieved by punch, incisional or shave
biopsy under local anaesthetic. Shave biopsy is undesir-
able in possible cutaneous melanoma. Exfoliative
cytology has a high diagnostic accuracy in NMSC, par-
ticularly where the tumour is ulcerated, and can be of use
to guide management where surgical biopsy may be dif-
ficult, such as in the very elderly. A tissue diagnosis
should also be obtained prior to radiotherapy (RT).
TABLE I
THE LOW RISK AND HIGH RISK
Low risk High risk
1. Nodular 1. Morphoeic/infiltrative
2. Superficial 2. Micronodular
3. Basosquamous
NON-MELANOMA SKIN CANCER: UK GUIDELINES
Recommendation
• Diagnosis of NMSC is usually clinical. Biopsy
(or exfoliative cytology) is recommended
where the clinical diagnosis is in doubt, or
where histological features may influence
treatment, and prior to radiation therapy (G)
High-risk features of NMSC
Some clinical and histological features are indicative of
aggressive tumour behaviour.
High-risk features of BCC for recurrence:
• Tumour size >2 cm
• Tumour site (the central face)
• Poorly defined clinical margins
• High-risk histological sub-type
• Histological features of aggression; peri-neural or
peri-vascular involvement
• Failure of previous treatment (the tumour is a
recurrence)
• Immunosuppression.
High-risk features of cSCC for recurrence and
metastasis:
• Size >2 cm
• Failure of previous treatment
• Immunosuppression
• Depth or invasion >2 mm thickness∗
• Clark level >4∗
• Peri-neural invasion∗
• Primary site ear or hair-bearing lip∗
• Poorly differentiated or undifferentiated∗ .
∗ into a future neck dissection approach. This will
Determined as high risk in Tumour–Node–Metastasis
(TNM) Classification of Malignant Tumours, 7th
Edition.
Of note, tumour depth is highly predictive for metas-
tasis and local recurrence. Cutaneous squamous cell
carcinoma less than 2 mm in depth has little or no
metastatic potential. In cSCC 2.1–6.0 mm thick, the
rate of metastasis is 4 per cent and for thickness
greater than 6.0 mm the rate is 16 per cent. Tumours
invading the sub-cutaneous fat have metastatic rates
up to 46 per cent.
NICE5 and the Royal College of Pathologists7 use
greater than 4 mm tumour depth or invasion into sub-
cutaneous fat as indicators for referral to the MDT.
The 7th edition of TNM Classification of Malignant
Tumours8 uses >2 mm tumour depth as a high-risk
factor. There is a wide range of malignant behaviour
of cSCC; head and neck surgeons are likely to deal
with a higher proportion of high-risk tumours.
S127
Recommendations
• Royal College of Pathologists minimum
datasets for NMSC should be adhered to in
order to improve patient care and help work-
force planning in pathology departments (G)
• Tumour depth is of critical importance in
identifying high-risk cSCC, and should be
reported in all cases (R)
Staging
The most widely adopted staging system for staging
cSCC and BCC is the TNM Classification of
Malignant Tumours, 7th Edition (Table II).8 Skin
cancers of the eyelid, and Merkel cell carcinomas are
included elsewhere.
Imaging to determine the extent of primary NMSC
may be indicated when peri-neural involvement (mag-
netic resonance imaging) or bony invasion (computed
tomography) is suspected. There is no evidence to
support cross-sectional imaging in the clinically node
negative patient.
In the clinically node positive patient, further assess-
ment and management is as per the guidelines set out
elsewhere in these guidelines, with the following add-
itional points for consideration.
• Cross-sectional imaging should include the
parotid.
• Clinically enlarged nodes should be examined ini-
tially by fine needle aspiration cytology (FNAC),
ideally ultrasound guided. This can be repeated
if negative, where clinical suspicion remains.
• Removal of a suspicious node for which FNAC
has been non-diagnostic can be carried out via a
considered incision which can be incorporated
enable accurate staging of a patient prior to thera-
peutic neck dissection.
TABLE II
T STAGING FOR CSCC AND OTHER CUTANEOUS
CARCINOMAS
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
T Is carcinoma in situ?
T1 Tumour 20 mm or less in greatest dimension and (with the
exception of BCC∗ ) with less than two high-risk
features∗
T2 Tumour greater than 20 mm in greatest dimension or (with
the exception of BCC∗ ) any size and with two or more
high-risk features∗
T3 Tumour with invasion of maxilla, mandible, orbit or
temporal bone
T4 Tumour with invasion of skeleton (axial or appendicular) or
peri-neural invasion of skull base
∗
Rarely applies to BCC and not accordingly included in staging
by The Royal College of Pathologists.
S128
• Sentinel node biopsy for the detection of metastat-
ic disease in high-risk cSCC is only used within
clinical trials.9
Recommendations
• Appropriate imaging to determine the extent
of primary NMSC is indicated when peri-
neural involvement or bony invasion is
suspected (R)
• In the clinically N0 neck, radiological imaging is
not beneficial, and a policy of watchful waiting
and patient education can be adopted (R)
The role of the multidisciplinary team
The importance of multidisciplinary working relation-
ships in the management of high-risk NMSC is para-
mount and patients should be treated by members of
a skin cancer MDT. Low-risk BCC is treated in some
regions by community practitioners as per updated
NICE guidance.5 Lesions above the clavicle are specif-
ically excluded from this group, and these patients
should receive treatment in secondary care. Cancer net-
works should establish two levels of MDTs to care for
patients, with high-risk cSCC and BCC being dis-
cussed either at a local skin MDT or regional specialist
skin cancer MDT. It is recognised that local and spe-
cialist MDT referral pathways will vary from region
to region.
Patients in the following groups should be discussed
at the skin cancer MDT as per NICE and Scottish
Intercollegiate Guidelines Network Guidance; input
from the head and neck cancer MDT will be appropri-
ate in the following groups:
• All patients with high-risk cSCCs, cSCCs and
BCCs that may involve the excision margins or
are recurrent.
• Patients suitable for Mohs surgery.
• Skin cancers in patients who are immunocom-
promised or those with genetic predisposition.
• Patients with metastatic SCC or BCC diagnosed at
presentation or on follow-up.
• Patients who may benefit from RT.
• Patients who may be eligible for entry into clinical
trials.
• Specific challenging management issues, such as
cognitive impairment or medical comorbidities.
Recommendation
• Patients with high-risk NMSC should be
treated by members of a skin cancer MDT in
secondary care (G)
C NEWLANDS, R CURRIE, A MEMON et al.
Treatment of the primary lesion
Surgical excision
Basal cell carcinoma. Excision with a predetermined
margin is the recommended treatment for the majority
of BCCs.10 Complete excision rates of 85 per cent with
a 3 mm clinical margin have been reported and of 95
per cent with a 4–5 mm margin. The stretch test, der-
moscopy, loupe magnification and prior curettage,
may improve definition of the tumour margin and
reduce incomplete excision rates. The deep margin
should include fat, but will be determined by tumour
extension – it can be clinically assessed at the time of
surgery.
Infiltrative and large BCCs have a higher risk of sub-
clinical tumour extension.
In the management of BCCs with a high risk of
recurrence, reconstruction should be delayed until
histological confirmation of clearance has been
confirmed, either by Mohs micrographic surgery
(MMS), or until the results of paraffin section are
available.
Recommendations
• Non-infiltrative BCCs <2 cm in size should be
excised with a margin of 4–5 mm. Smaller
margins (2–3 mm) may be taken in sites
where reconstructive options are limited,
when reconstruction should be delayed (R)
• Where there is a high risk of recurrence,
delayed reconstruction11 or MMS should be
used (R)
Cutaneous squamous cell carcinoma. Surgical excision
with a predetermined clinical margin is the recom-
mended treatment for the majority of cSCC. For clinic-
ally well-defined, low-risk tumours, a margin of 4 mm
will achieve histological clearance in over 95 per cent
of cases. In high-risk cSCC, the evidence on peripheral
margins required is limited, but at least 6 mm should be
included in the resection. The deep margin on the scalp
should include the galea at least; the peri-osteum and
outer table should be resected if there is clinical or
radiological evidence of involvement. Conventional
intra-operative frozen section is less accurate than par-
affin section and is no longer recommended. The con-
firmation of histological clearance can be confirmed by
awaiting the results of paraffin section, before recon-
struction is undertaken. Both excised BCC and cSCC
specimens should be marked for orientation in case
further resection is required.
Mohs micrographic surgery. Mohs micrographic
surgery is a precise technique which combines
staged resection with comprehensive histological
examination of the surgical margin. It is the treatment
of choice in high-risk BCC and not only offers
NON-MELANOMA SKIN CANCER: UK GUIDELINES
superior tumour control (97 per cent five-year cure
rates), but better cosmetic outcomes as tissue
removal is minimised. Mohs micrographic surgery
is used less often for high-risk SCC due to concerns
about the possible presence of in transit metastases
and skip lesions, and the more challenging histo-
logical margin interpretation (permanent sections
are more accurate than frozen sections).
Disadvantages of MMS include the length of the pro-
cedure (which is carried out under local anaesthetic),
the need for special equipment and training and the
relatively high cost. The availability of the procedure
in the UK is at present limited.
Recommendations
• Surgical excision of low-risk cSCC with a
margin of 4 mm or greater is the treatment of
choice (R)
• High-risk cSCC should be excised with a
margin of 6 mm or greater (R)
• Mohs micrographic surgery has a role in some
high-risk cSCC cases following MDT
discussion (R)
• Delayed reconstruction should be used in
high-risk cSCC (G)
• Intra-operative conventional frozen section in
cSCC is not recommended (G)
Destructive techniques
Curettage and cautery. This can be used by experienced
practitioners for small (<4 mm), well-defined BCC
with non-aggressive histology in non-critical sites
with a five-year cure rate of up to 97 per cent.
Curettage and cautery is used in some centres to treat
small (<1 cm) low-risk cSCCs with excellent cure
rates, but histological clearance cannot be confirmed.
Its use should be confined to experienced practitioners
in the technique, employing careful case selection cri-
teria. Curettage and cautery is not indicated in recurrent
or high-risk NMSC.
Cryosurgery. Cryosurgery is used in low-risk BCC.
Disadvantages include scarring, difficulty in asses-
sing recurrence and lack of tissue diagnosis or
proof of tumour clearance. Good short-term cure
rates have been reported for small histologically con-
firmed cSCC treated by cryosurgery in experienced
hands. Prior biopsy is necessary to establish the diag-
nosis histologically. For this reason, caution should
be exercised in the use of cryotherapy for cSCC
although it may be an appropriate technique for
selected cases especially in very elderly patients
and in specialised centres. Cryosurgery is not appro-
priate for locally recurrent disease or high-risk
tumours.
S129
Photodynamic therapy. This therapy is effective in low-
risk superficial BCC, but with lower oncologic efficacy
than surgery in nodular BCC. It is not recommended
for other BCC sub-types or for cSCC.
Topical 5 per cent imiquimod. This is an immune
response modifier which is licensed for and effective
in the treatment of small primary superficial BCC.
Vismodegib. This drug is licensed for locally advanced
or metastatic BCC not suitable for surgery or RT. This
new drug is an antagonist for the smoothened G-
protein-coupled receptor molecule, and thus inhibits
the aberrant signalling pathway involving Hedgehog
(Hh) genes. Early trials show efficacy in 50 per cent
of BCCs with mean duration of response around nine
months. It is a suitable treatment in recurrent, inoper-
able BCCs post-RT or in patients with Gorlin’s syn-
drome, and in the very rare occurrence of metastatic
BCC.
Radiotherapy in primary NMSC
Radiotherapy is an alternative to surgery for primary
BCC and cSCC of the head and neck region in the fol-
lowing scenarios:
• Elderly or frail patients
• Anatomical sites where RT is likely to lead to a
superior cosmetic or functional outcome
• Surgery is contraindicated
• Patient choice.
At most head and neck sites, cosmetic outcomes and
cure rates with RT are inferior to excisional surgery.
Radiotherapy is normally not used in the following
circumstances:
• Patient age over 50 years, due to the risk of second
malignancies and inferior cosmetic outcome
• Sites of previous RT
• Cartilage or bone involvement due to risk of
radionecrosis
• Over the lateral half of the upper eyelid due to risk
of lacrimal gland damage.
Basal cell carcinoma and cSCC are usually treated
with low-energy (KV) X-rays, but may be treated
with electrons. Alternatively, high-energy (MV) X-
rays may be used in the presence of deep extension
or tumour fixation. Common fractionation schedules
range from five fractions in one week for lesions
greater than 2–3 cm; to 9–10 fractions in two to three
weeks for intermediate size; and 20–30 fractions over
four to six weeks for very large (>6 cm) lesions or
where regional lymph node irradiation is also required.
The dose is usually higher and a larger margin included
in the treatment field when treating cSCC than
BCC.12,13
S130
Recommendation
• Radiotherapy is an effective treatment for
primary BCC and cSCC (R)
Incomplete margins of excision
Incomplete excision of BCC can occur in the setting of
high-risk tumour factors, low operator expertise and
when multiple tumours are removed at the same pro-
cedure. Incompletely excised NMSC should be dis-
cussed at the MDT, as should those with a margin of
excision less than 1 mm. Options for management
include observation (many low-risk tumours will not
recur), re-excision (by standard surgery or with margin-
al control) and adjuvant treatment (radiation therapy or
topical therapy)
British Association of Dermatology recommenda-
tions for consideration of re-excision of transected
BCC include:
• Anatomically critical site
• Infiltrative histology
• Deep margin involvement
• Flap or graft reconstruction.
Incompletely excised high-risk cSCC should be re-
excised to reduce the risk of recurrence and metastasis.
In closely excised high-risk cSCC, re-excision or the
use of adjuvant RT should be discussed at the MDT
and may be influenced by local anatomy, and recon-
structive factors. Where further treatment of NMSC is
indicated and re-excision is not possible, adjuvant RT
is indicated to decrease recurrence rates.14,15
If a margin is involved by superficial BCC only,
topical imiquimod may be indicated.
Recommendations
• Re-excision should be carried out for
incompletely excised high-risk BCC or where
there is deep margin involvement (R)
• Incompletely excised high-risk cSCC should
be re-excised (R)
• Further surgery should involve confirmed
marginal clearance before reconstruction (R)
Management of regional metastatic CSCC
Patterns of metastasis
The overall regional metastatic rate of cSCC in a UK
population has been reported at around 5 per cent.16
These rates can be higher in the presence of adverse
histological features; for instance, 33 and 47 per cent
for poor differentiation or peri-neural infiltration,
C NEWLANDS, R CURRIE, A MEMON et al.
respectively. Tumour thickness is strongly correlated
with risk of nodal metastasis. The presence of metastat-
ic nodal disease is associated with a five-year survival
of 35 per cent.
Lymph node metastases of NMSC of the head
and neck are known to follow different pathways to
the classically understood patterns of mucosal malig-
nancies of the upper aerodigestive tract (Figure 1).
The parotid nodes and the superficial lymphatic
system need to be addressed, in contrast to mucosal
head and neck mucosal malignancies. Sentinel node
biopsy studies have shown a high lack of concordance
between the primary skin site and the first echelon
node. The external jugular node is of particular rele-
vance as it is not included in standard neck dissections
for head and neck squamous cell carcinoma.
Over 50 per cent of cSCC occurs on the anterior
scalp and forehead and the ears, and the parotid is the
site for up to 70 per cent of metastasing cSCC.
Where the parotid is involved (P+), there is an
increased chance of the neck containing occult and
overt metastases (10–35 per cent). In the P+N+ scen-
ario, the incidence of metastases in level V approaches
30 per cent.
N+ P0 disease is seen where the primary site was the
face or upper neck or posterior scalp. The posterior
scalp is the site for 5 per cent of cSCC, and tumours
here will metastasise initially commonly to post-auricu-
lar, occipital or level V nodes.17,18 Resection of
FIG. 1
Patterns of metastasis of cSCC to the external jugular node and the
superficial lymphatics.
NON-MELANOMA SKIN CANCER: UK GUIDELINES
structures such as the facial nerve, the internal jugular
vein, the accessory nerve and the sternocleidomastoid
muscle are required in a nodal dissection in the pres-
ence of invasion by the malignant process.
Management of nodal involvement
Surgery is the primary mode of treatment for estab-
lished nodal involvement and adjuvant RT may
improve survival in high-risk cases. The dissection
employed should include established nodal involve-
ment and extend to those levels where there is a high
risk of occult disease. In most cases, parotid surgery
will involve a superficial parotidectomy; deep lobe or
facial nerve involvement will require more extensive
resection.
Recommendations
• P+ N0 disease:
Resection should include involved parotid
tissue, combined with levels I–III neck
dissection, to include the external jugular
node (R)
• P+ N+ disease:
Resection should include level V if that level is
clinically or radiologically involved (R)
Adjuvant RT should include level V if not
dissected (R)
• P0 N+ disease:
Anterior neck disease should be managed
with a levels I–IV neck dissection to include
the external jugular node (R)
P0 N+ Posterior echelon nodal disease (i.e.
occipital or post-auricular) should undergo
dissection of levels II–V, with sparing of
level I (R)
Consider treatment of the ipsilateral parotid,
if the primary site is the anterior scalp, temple
or forehead (R)
Role of RT in P+ and/or N+ disease
Retrospective studies suggest that locoregional control
and survival are improved by adjuvant RT in cases of
cSCC where neck involvement is staged greater than
N1, or where there is extracapsular spread. Of note,
ECS is seen in up to 70 per cent of head and neck
cSCC nodal dissection, and therefore consideration
can be given to more selectivity in nodal dissection,
as post-operative RT will be indicated for the majority
of patients.19
Follow-up
Follow-up in secondary care may detect local recur-
rence, regional metastasis and new skin cancers at an
earlier stage. Of note, the risk of a second BCC is 44
per cent, and up to 50 per cent of Australian cSCC
patients develop a second cSCC within two years.
S131
Minimisation of immunosuppression in an organ trans-
plant patient with multiple or recurrent high-risk cSCC
should be considered by the MDT in conjunction with
the patient’s relevant physician. Oral retinoids can be
used for secondary prevention skin cancers in the
immunosuppressed.
Recommendations
• All patients should receive education in self-
examination and skin cancer prevention
measures (G)
• Patients who have had a single completely
excised BCC or low-risk cSCC can be
discharged after a single post-operative visit (G)
• Patients with an excised high-risk cSCC
should be reviewed three to six monthly for
two years, with further annual review
depending upon clinical risk (G)
• Those with recurrent or multiple BCCs
should be offered annual review (G)
Key points
• Diagnosis of NMSC is usually clinical.
• Excisional surgery with predetermined margins is
the treatment of choice for the majority of cases.
• Imaging is recommended in large primary
tumours, but does not have a role where the
regional nodes are clinically N0.
• Reconstruction should be delayed in high risk
NMSC.
References
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Address for correspondence:
Carrie Newlands,
Department of Oral and Maxillofacial Surgery,
Royal Surrey County Hospital,
Guildford, UK
E-mail: carrienewlands@googlemail.com
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S133–S141. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000852

Head and neck melanoma (excluding ocular

melanoma): United Kingdom National
Multidisciplinary Guidelines

O A AHMED1, C KELLY2
1
Department of Plastic and Reconstructive Surgery, The Newcastle upon Tyne Hospitals NHS Trust, Newcastle
upon Tyne, and 2Northern Centre for Cancer Care and Newcastle University, Freeman Hospital, Newcastle upon
Tyne, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the United Kingdom. This paper provides consensus recommendations on the management of
melanomas arising in the skin and mucosa of the head and neck region on the basis of current evidence.

Recommendations
• At-risk individuals should be warned about the correlation between ultraviolet radiation (UVR) exposure and
skin cancer, and should be given advice on UVR protection. (R)
• Dermatoscopy can aid in the diagnosis of cutaneous melanoma. (R)
• Histological examination after biopsy is essential to confirm the diagnosis and the tumour thickness. (G)
• Excisional biopsy is method of choice. (G)
• Staging investigations can be performed for both regional and distant disease. (R)
• Scanning (computed tomography (CT) and/or magnetic resonance imaging) is recommended for patients with
high-risk melanoma. (G)
• Patients with signs or symptoms of disease relapse should be investigated by imaging. (R)
• Imaging of the brain should be performed in patients who have stage IV disease. (G)
• Patients with melanoma of unknown primary should be thoroughly examined and investigated for a potential
primary source. (R)
• Primary cutaneous invasive melanoma should be excised with a surgical margin of at least 1 cm. (G)
• The maximum recommended excision margin is 3 cm. (R)
• The actual margin of excision depends upon the depth of the melanoma and its anatomical site. (G)
• Ultrasound-guided fine needle aspiration (FNA) or core biopsy of suspected lymphadenopathy is more accurate
than ‘blind’ biopsy. (R)
• Open biopsy should only be performed if FNA or core biopsy is inadequate or equivocal. (R)
• Prior to lymph node dissection, staging by CT scan should be carried out. (R)
• If parotid disease is present without neck involvement, both parotidectomy and neck dissection should ideally
be performed. (R)
• There is no role for elective lymph node dissection. (R)
• Sentinel lymph node biopsy (SLNB) can be considered in stage IB and above by specialist skin cancer
multidisciplinary teams. (G)
• Patients should be made aware that SLNB is a staging procedure, and should understand that it has, as yet, no
proven therapeutic value. (R)
• All patients with cutaneous melanoma should have their original tumour checked for BRAF gene status, and
their subsequent targeted biological therapy based on this. (R)
• Patients who develop brain metastases should be considered for stereotactic radio-surgery. (R)

Cutaneous melanoma of the head and neck

Introduction
Cutaneous melanoma, also known as cutaneous malig-
nant melanoma, is a malignant tumour of neural crest-
derived cutaneous melanocytes. The incidence of
melanoma has been increasing rapidly for the last few
decades in most parts of the world. It is the fifth
commonest cancer in the UK, with a male:female
ratio of 10:11. The number of melanoma cases
doubled in this country over the three decades follow-
ing 1970. Over that same period the prognosis dramat-
ically improved. This improvement is mostly
attributable to a higher proportion of thinner tumours
as a result of earlier diagnosis, and reflects the
S134
considerable effort expended in raising public and pro-
fessional awareness over that period. Although melan-
oma is the major cause of skin cancer mortality, it is
usually curable if treated at an early stage. Melanoma
in its advanced stages remains largely resistant to cur-
rently available treatments, although in the last five
years, new targeted biological agents and immunother-
apies have offered the potential for improved survival.
Aetiology and risk factors
Melanomas can arise in pre-existing naevi, or de novo
in normal skin. Like most tumours, the aetiology of
melanoma is complex and not fully understood. It is,
however, thought to be caused by ultraviolet radiation
(UVR) in susceptible individuals. It is estimated that
around 86 per cent of melanomas in the UK in 2010
were linked to exposure to UVR from the sun and
sun-beds.1 Fair-skinned individuals who burn easily
in the sun, have fair or red hair, and have a tendency
to freckle are about three times more likely to
develop melanoma. A number of case–control studies
conclude that intense burning sun exposure of unaccli-
matised white skin is a major risk factor for cutaneous
melanoma. Migration studies show that exposure to
intense UVR at a young age may be particularly
important. This is in contradistinction to squamous
cell and basal cell carcinomas, which are associated
with chronic, long-term sun exposure. Patients with
xeroderma pigmentosum have a significantly higher
risk of all types of skin cancer, including melanoma,
as a result of inability to repair the DNA damage
induced by UVR.
Recommendation
• At-risk individuals should be warned about
the correlation between UVR exposure and
skin cancer, and should be given advice on
UVR protection (R)
While it is understood that melanoma is related to UVR
exposure, it is not clear why the body site distribution
of melanoma is different to other sun-related cancers
such as cutaneous squamous cell carcinoma. This sug-
gests that the pattern of UVR exposure is important,
with sites that are intermittently exposed being more
at risk than continually exposed sites. The gaps in
our knowledge of the aetiology have recently been crit-
ically evaluated.
Other risk factors include a large number of banal
naevi, a tendency to freckle, and more atypical or dys-
plastic naevi.2 About 2 per cent of melanoma patients
have a positive family history in one or more first
degree relatives. The major melanoma susceptibility
gene identified to date is CDKN2A gene. Mutations
in this gene are found in 10–30 per cent of melanoma
patients with a positive family history. Melanoma is
O A AHMED, C KELLY
more prevalent in those of high socio-economic
status, but the converse applies to mortality.
Clinical presentation
Cutaneous melanoma is divided into subtypes on the
basis of clinical features and pathology.
Superficial spreading melanoma (SSM). This is the most
frequently encountered type of melanoma; characteris-
tically an asymmetrical pigmented lesion with irregular
borders, irregular pigmentation and sometimes an
irregular outline. Patients may have noted growth, a
change in sensation and/or colour, crusting, bleeding
or inflammation of the lesion. The duration of the
symptoms varies from a few months to several years.
Nodular melanoma (NM). The second most common
type of melanoma is NM. This usually has a shorter
presentation and a greater tendency to bleed and/or
ulcerate.
Lentigo maligna melanoma (LMM). The next in fre-
quency is the type that occurs most often in sun-
damaged skin on the head and neck of older patients.
This is the only variety that has a clearly recognised
and often lengthy pre-invasive (in situ) lesion termed
lentigo maligna (LM) before progressing in some
instances to an invasive melanoma (LMM).
Acral lentiginous melanoma (ALM). The least common
type of melanoma in the UK is the ALM. This
occurs on sites, including the palms, soles and
beneath the nails. It is the most common melanoma
found in African and Asian populations.
Desmoplastic neurotropic melanoma. This type is asso-
ciated with higher local recurrence than other forms
of melanoma. This is thought to be a consequence of
its propensity for peri-neural spread. Desmoplastic
neurotropic melanoma is predominantly found in the
head and neck.
Assessment and staging
Suspicious pigmented lesions are best examined in a
good light with or without magnification and should
be assessed using the seven-point checklist3 (Table I)
or ABCDE systems (Table II). The presence of any
major feature in the seven-point checklist, or any of
the features in the ABCDE system, is an indication
for referral. The presence of minor features should
TABLE I
SEVEN POINT CHECKLIST FOR PIGMENTED SKIN
LESIONS
Major features Minor features
Change in size of lesion Inflammation
Irregular pigmentation Itch/altered sensation
Irregular border Lesion larger than others
Oozing/crusting of lesion
HEAD AND NECK MELANOMA: UK GUIDELINES S135

TABLE II TABLE III

THE ABCDE CHECKLIST FOR PIGMENTED SKIN TNM STAGING SYSTEM FOR CUTANEOUS MELANOMA
LESIONS
T classification Thickness Ulceration status/
A Geometrical Asymmetry in two axes mitoses
B Irregular Border
C At least two different Colours in lesion Tis N/A N/A
D Maximum Diameter >6 mm T1 ≤1.0 mm a: w/o ulceration and
E Elevation of lesion mitoses <1/mm2
b: with ulceration or
mitoses ≥1/mm2
increase suspicion. Some melanomas will have no T2 1.01–2.0 mm a: w/o ulceration
b: with ulceration
major features. T3 2.01–4.0 mm a: w/o ulceration
b: with ulceration
T4 >4.0 mm a: w/o ulceration
Clinical diagnosis of melanoma can be difficult and the b: with ulceration
accuracy of diagnosis varies according to a clinician’s N classification No of metastatic Nodal metastatic
level of experience, with reports of variation in sensi- nodes mass
N0 0 nodes N/A
tivity from 50 to 86 per cent. High magnification der- N1 One node a: micrometastasis∗
matoscopy is more sensitive than non-dermatoscopic b: macrometastasis†
diagnosis, when used by those trained and experienced N2 Two to three nodes a: micrometastasis∗
b: macrometastasis†
in the technique.4 Hand-held (lower magnification) c: in-transit met(s)/
dermatoscopy improves diagnostic accuracy in those satellite(s) without
trained to be ‘expert’, but it may decrease diagnostic metastatic nodes
N3 Four or more
sensitivity of ‘non-expert’ or untrained dermatologists. metastatic nodes,
or matted nodes,
Diagnostic biopsy. The thickness of cutaneous melan- or in-transit
oma greatly influences both its treatment and its prog- met(s)/
satellite(s) with
nosis. It is essential, therefore, to obtain a full-thickness metastatic
biopsy of suspected lesions. Excisional biopsy is the node(s)
preferred technique, and is aimed at excising the M classification Site Serum lactate
dehydrogenase
lesion with a 2–5 mm peripheral margin, including a (LDH)
cut-off of subdermal fat. This allows accurate assess- M0 0 sites N/A
ment of the tumour thickness and depth of penetration, M1a Distant skin, Normal
subcutaneous, or
without transgressing tumour boundaries. Excisional nodal mets
biopsy may not be practical when the lesion is large M1b Lung metastases Normal
or located near structures such as an eyelid or lip. M1c All other visceral Normal
metastases
Punch biopsy is an alternative where excision biopsy Any distant Elevated
could lead to significant disfigurement. A punch metastases
biopsy is usually performed with a 2–4 mm biopsy ∗
Micrometastases are diagnosed after sentinel lymph node biopsy
punch at the thickest or highest part of the lesion. and completion lymphadenectomy (if performed)
Incisional biopsy is not usually recommended, but † Macrometastases are defined as clinically detectable nodal
metastases confirmed by therapeutic lymphadenectomy or when
the indications are the same as those for punch nodal metastasis exhibits gross extracapsular extension
biopsy. Again, it should be performed at the thickest
or highest part of the lesion and must reach the full
depth of the lesion (mitoses/mm2) is now considered an important inde-
pendent prognostic indicator, with an inverse correlation
Recommendations between mitotic rate and survival. The mitotic rate
replaces Clark’s level of invasion as a primary criterion
• Dermatoscopy can aid in the diagnosis of for separating T1 tumours into T1a and T1b.
cutaneous melanoma (R)
• Histological examination after biopsy is
essential to confirm the diagnosis and the Anatomical staging
tumour thickness (G)
• Excisional biopsy is method of choice (G) Imaging considerations. Staging investigations for
regional lymph node metastases are often performed,
and may comprise computed tomography (CT), magnetic
resonance imaging (MRI), and/or ultrasound, depending
Staging. The latest revisions to the staging of cutaneous upon local protocols. The use of scans to detect distant
melanoma were published in the 7th Edition of the metastasis is indicated in patients with high-risk melan-
American Joint Committee on Cancer (AJCC) in 2009 oma (stages IIC, IIIB, IIIC and stage IIIA with a macro-
(Table III).5 Of note, primary tumour mitotic rate scopic sentinel lymph node), and in patients with new
S136 O A AHMED, C KELLY

TABLE IV
CLINICAL AND PATHOLOGICAL STAGING FOR CUTANEOUS MELANOMAS
Clinical staging∗ Pathological staging†

0 Tis N0 M0 0 Tis N0 M0
IA T1a N0 M0 IA T1a N0 M0
IB T1b N0 M0 IB T1b N0 M0
T2a N0 M0 T2a N0 M0
IIA T2b N0 M0 IIA T2b N0 M0
T3a N0 M0 T3a N0 M0
IIB T3b N0 M0 IIB T3b N0 M0
T4a N0 M0 T4a N0 M0
IIC T4b N0 M0 IIC T4b N0 M0
III Any T N > N0 M0 IIIA T1–4a N1a M0
T1–4a N2a M0
IIIB T1–4b N1a M0
T1–4b N2a M0
T1–4b N1b M0
T1–4b N2b M0
T1–4b N2c M0
IIIC T1–4b N1b M0
T1–4b N2b M0
T1–4b N2c M0
Any T N3 M0
IV Any T Any N M1 IV Any T Any N M1
∗
Clinical staging includes microstaging of the primary melanoma and clinical and/or radiologic evaluation for metastases. By convention, it
should be used after complete excision of the primary melanoma with clinical assessment for regional and distant metastases
† Pathological staging includes microstaging of the primary melanoma and pathological information about the regional lymph nodes after
partial or complete lymphadenectomy. Pathological stage 0 or IA patients are the exception; they do not require pathological evaluation
of their lymph nodes

symptoms, anaemia, elevated lactate dehydrogenase or a
chest X-ray abnormality. Computed tomography scan-
ning is used for the evaluation of potential metastatic
sites in the lungs, bones, liver and lymph nodes.
Imaging of the brain is recommended in patients with
stage IV, but is optional in stage III disease. Positron
emission tomography (PET)-CT is more accurate than
CT or MRI alone in the diagnosis of metastases. It
should complement conventional CT and MRI imaging
in patients who have distant metastases and where surgi-
cal resection is being considered.
Recommendations
• Staging investigations can be performed for
both regional and distant disease (R)
• Scanning (CT and/or MRI) is recommended
for patients with high-risk melanoma (G)
• Patients with signs or symptoms of disease
relapse should be investigated by imaging (R)
• Imaging of the brain should be performed in
patients who have stage IV disease (G)
Unknown primary. The patient presenting with regional
or visceral metastatic melanoma of unknown primary
(MUP) origin should be seen by a dermatologist for a
skin examination, an ophthalmologist for examination
of the eye, and a head and neck surgeon for visualisa-
tion of the upper aerodigestive tract. Staging investiga-
tions should be carried out, including PET-CT to detect
occult metastases. In 10–20 per cent of patients with
regional or visceral melanoma metastases, the
primary melanoma is never found. Such patients
should be treated as if they have regional or visceral
metastases from a known primary melanoma.6 It has
been suggested that the most likely explanation for
MUP is immune-induced regression of the primary
tumour, and this may be the reason for the slightly
better outcomes in such patients.
Recommendation
• Patients with a melanoma of unknown
primary origin should be thoroughly
examined and investigated for a potential
primary source (R)
Management
Surgery for primary disease
Wide local excision. This remains the most effective
treatment for primary cutaneous melanoma.2,7 The
optimal width of excision margins has been conten-
tious.8,9 Current treatment guidelines are based on a
relatively small number of prospective randomised
trials.10–12 The current recommended excision
margins for cutaneous melanoma in the UK are as
follows:
• In situ melanoma (LM): 5 mm peripheral margins
• Lesions <1 mm thick: 1 cm excision margins
• Lesions 1–2 mm thick: 1–2 cm excision margins
• Lesions 2.1–4 mm thick: 2–3 cm margins (2 cm
preferred)
• Lesions thicker than 4 mm: 2–3 cm margins.
HEAD AND NECK MELANOMA: UK GUIDELINES
It should be stressed that these recommendations are
for cutaneous melanomas in all body sites; in the
head and neck region, anatomical restrictions and cos-
metic considerations may preclude even a 1 cm margin.
In these circumstances, however, the width of excision
should remain uniform. For example, if a clear margin
of only 8 mm is possible near to an eyelid or an ear, the
rest of the peripheral surgical margins should also be
8 mm.
Recommendations
• Primary cutaneous invasive melanoma should
be excised with a surgical margin of at least
1 cm (G)
• The maximum recommended excision margin
is 3 cm (R)
• The actual margin of excision depends upon
the depth of the melanoma and its anatomical
site (G)
Mohs micrographic surgery (MMS). Mohs micrographic
surgery may have a role in the primary treatment of
cutaneous melanoma of the head and neck, especially
that of the face.13 There is growing evidence of the effi-
cacy of MMS in comparison to traditional surgery but
the majority of reports compare MMS with historical
controls. Further study, in the form of prospective com-
parative trials, is required before firm recommendations
can be made regarding the use of MMS.
Reconstruction. When possible, the surgical defect after
wide local excision should be closed primarily. If
primary closure is not possible, reconstruction by
local flaps or skin grafts will be required. Local flaps
are the preferred option when the surgical defect is on
the face, because of a superior aesthetic outcome.
Rarely, distant flaps will be required for complex or
very large surgical defects. If there is any doubt as to
the adequacy of surgical clearance, definitive recon-
struction should be delayed pending histological
confirmation.
Surgery for regional disease
The regional lymph node basin in head and neck cuta-
neous melanoma comprises the nodes found in the
parotid gland (superficial portion), neck levels I–V,
the occipital nodes, mastoid nodes and pre-auricular
nodes. There may be clinically apparent lymphadenop-
athy, representing metastatic melanoma, or occult
metastases in the head and neck nodes.
Clinical lymphadenopathy. When patients present with a
neck mass or a radiologically identified suspicious
node(s) a tissue diagnosis should be obtained. The pre-
ferred stepwise diagnostic algorithm to follow is: (1)
palpable lymph node in the neck or radiologically iden-
tified suspicious node; (2) ultrasound-guided or
S137
clinically-guided FNA; (3) ultrasound-guided core
biopsy; (4) open biopsy.
Fine needle aspiration is more accurate when performed
with ultrasound guidance, and this should be subsequently
performed if a clinically guided FNA is non-diagnostic. If
an open biopsy is performed, the incision should be placed
in a manner which permits subsequent excision of the
biopsy tract if a neck dissection is necessary. If metastatic
melanoma is confirmed, lymphadenectomy of the
involved nodal basin should be performed.
The extent of lymphadenectomy performed for melan-
oma is determined by the location of the primary, the
location of the neck disease, and the general fitness of
the patient. If parotid lymphadenopathy is present, a
neck dissection should also be performed as a high pro-
portion of patients with parotid lymph node involvement
will have occult cervical metastases. If neck disease is
present without parotid involvement then the location
of the primary should be considered. If the draining
basin of that primary site is likely to pass through the
parotid gland, a concomitant superficial parotidectomy
should be considered. It is reasonable to perform a select-
ive neck dissection for some melanoma sites that have
metastasised to the neck when there is low volume,
mobile lymphadenopathy. For example, omitting exci-
sion of level IA and IB neck nodes for a well-lateralised
occipital melanoma would be accepted management.
Recommendations
• Ultrasound-guided FNA or core biopsy of
suspected lymphadenopathy is more accurate
than ‘blind’ biopsy (R)
• Open biopsy should only be performed if FNA
or core biopsy is inadequate or equivocal (R)
• Prior to lymph node dissection, staging by CT
scan should be carried out (R)
• If parotid disease is present without neck
involvement, both parotidectomy and neck
dissection should ideally be performed (R)
• If neck disease is present without parotid
involvement, parotidectomy should be
considered if the lymphatic drainage of the
primary site is likely to have passed through
the parotid gland (R)
Occult lymph nodal disease. The most accurate means of
staging the regional lymph nodes in head and neck mel-
anoma is by sentinel lymph node biopsy (SLNB). This
staging tool has a learning curve and involves the admin-
istration of a radiocolloid into the site of the excision
biopsy. Pre-operative lymphoscintigraphy identifies the
approximate location of the sentinel nodes and the
intra-operative use of blue dye and a gamma probe
S138
aids in location of the sentinel node(s). The removed
sentinel nodes are histologically examined with mul-
tiple sections and immunohistochemical stains for the
presence of occult metastases. Sentinel lymph node
biopsy identification of regional lymph node metastasis
should be followed by lymphadenectomy of the at-risk
nodal basin.
Whether or not SLNB is performed for staging the
regional lymph nodes is a matter for local policy.
Sentinel lymph node biopsy provides highly accurate
staging information but there is controversy as to
whether or not it improves disease-specific survival.
The long-term results of the Multicentre Selective
Lymphadenectomy Trial-I (MSLT-I) indicate that
SLNB is associated with improved disease-free survival
for patients with intermediate thickness (1.2–3.5 mm)
and thick (≥3.5 mm) melanomas,14 but this has been
questioned in a recent editorial in the British Medical
Journal.15 Furthermore, there is the question of biologic-
al false-positivity.16 Some clinical trials require informa-
tion on disease stage and an SLNB can provide this
information. Sentinel lymph node biopsy has replaced
elective lymph node dissection in melanoma and there
are few indications to perform the latter.
The Options Grid Collaborative, based at Dartmouth
University, is an organisation which attempts to
improve shared decision-making between healthcare
professionals and patients, their carers and families.
They produced, in collaboration with the National
Institute for Health and Care Excellence, three tools
to try and help patients with practical decision-
making in managing melanoma. These can be found
at http://optiongrid.org
Recommendations
• There is no role for elective lymph node
dissection (R)
• Sentinel lymph node biopsy can be considered
in stage IB and above by specialist skin cancer
multidisciplinary teams (G)
• Patients should be made aware that sentinel
lymph node biopsy is a staging procedure, and
should understand that it has, as yet, no
proven therapeutic value (R)
Metastatic disease. Distant melanoma metastases
occur preferentially and earliest in intra-abdominal
organs, liver, lung, brain and bone. Whilst these are
the commonest sites, metastases to almost every
organ and tissue have been reported.
Distant metastases can be divided into two groups:
metastases already established at presentation of the
primary (stage IV disease) and metastases that subse-
quently become apparent. Metastases at presentation
carry the worst prognosis, while for delayed metastases
O A AHMED, C KELLY
the prognosis improves in direct proportion to the time
taken for the metastasis to develop. In practice the ques-
tions to be addressed are what, if any, improvement in
survival time may be gained from treatment of meta-
static disease and what symptomatic improvement
will occur?
Treating metastases in patients with distant metasta-
ses confirmed at presentation (stage 4 disease) has
proved very disappointing. Survival rates in such indi-
viduals have not improved over the last two decades.
Resection of late-appearing metastases to non-liver
intra-abdominal organs or gastro-intestinal mucosa
yields the best improvement with a disease-free sur-
vival in the region of 23 months compared with a
median survival of only 12 months if untreated.17
Patients undergoing surgical resection of late-appear-
ing metastatic melanoma to the liver also have
improved disease-free survival compared with untreat-
ed patients.18,19
Surgical resection of pulmonary metastases and soli-
tary brain metastases from melanoma may yield a sur-
vival advantage of a few months more than any other
method of dealing with these lesions. Stereotactic
radiosurgery (SRS) for brain metastases also offers
some patients extended survival. Early treatment of
spinal cord secondaries can preserve mobility. Bone
metastases are associated with short survival irrespect-
ive of treatment.
Biological markers have been studied extensively in
metastatic melanoma with regard to prognosis and as a
guide to resectability of metastases. Of these, lactate
dehydrogenase (LDH) and the c-kit mutation may be
helpful. A high serum LDH level suggests a large
disease burden and a poor result from treatment of
metastases.
Aggressive surgical treatment of distant metastases
from melanoma at any site must be carried out on
highly selected patients and, even then, it is best
regarded as a palliative procedure, usually improving
survival by only a matter of months. Nevertheless,
quite long remissions may be obtained in fit patients
with apparently solitary, or oligometastatic, disease.
Non-surgical treatment
Primary tumour. There is no established role for
primary radiotherapy (RT) (instead of surgery) in the
management of early stage (stages Ia, b and IIa, b, c)
malignant melanoma, other than in elderly patients
with extensive facial LMM. It is unlikely that this situ-
ation will change in the foreseeable future. Similarly,
chemotherapy, biological agents and immunotherapy
have no proven place in the management of early
stage melanoma.20
Regional disease. In patients with stage III (nodal) or
IV (M1) disease, the prognosis is significantly worse.
Surgery remains the key initial treatment with the
goal of securing local control, even in the setting of
metastatic disease. There is no established role for RT
HEAD AND NECK MELANOMA: UK GUIDELINES
in the management of patients with micrometastatic
nodal disease (N1a, N2a). These patients are treated
with surgery alone (±entry into studies of adjuvant
systemic therapies). Recent adjuvant trials in
malignant melanoma have included those testing
immunotherapies (interferon, interleukin-2, peptide
gp100:209–217(210 M), CanvaxinTM) and anti-angio-
genic agents, such as bevacizumab (Avastin).20 For
patients with macrometastatic nodal disease (N1b,
N2b), there is no consensus that RT is beneficial fol-
lowing surgery, but for patients with cervical lymph
node disease it is frequently used. There is no currently
defined role for chemoradiation in this setting. The
findings of the Phase III TROG 02.01 trial suggest
that entry to an adjuvant systemic therapy trial may
be a preferable alternative to adjuvant RT.21
Distant metastases. Patients with established meta-
static melanoma are treated with palliative intent and
should be referred to specialist melanoma units.
The chemotherapy management options for metastat-
ic melanoma have greatly expanded in the last five years
with the introduction of biologically targeted agents.22
About 50 per cent of melanomas show a mutation in
the BRAF gene, with valine substituted for glutamate
at codon 600, and this mutation is known as V600E or
V600K. If this mutation is present then patients will
have a 60–70 per cent chance of responding to a
BRAF inhibitor drug such as vemurafenib23 or dabrafe-
nib. Those patients who develop the most slowly but
continued response to these BRAF inhibitors appear to
achieve a more sustained response when compared
with those patients who develop a very rapid tumour
clearance. One potential sideeffect of these drugs,
which must be monitored, is the development of squa-
mous cell carcinoma of the skin.
The second major advance in the management of
metastatic melanoma was the introduction of immuno-
therapy. Ipilimumab is a monoclonal antibody which
targets cytotoxic T lymphocyte-associated protein 4
(CTLA-4) which is a protein receptor which can be
made to switch off cytotoxic T lymphocytes (CTLs)
by melanoma cells. Ipilimumab removes this brake on
the immune response and allows the CTLs to recognise
and destroy melanoma cells. This agent’s efficacy does
not depend on the patient’s BRAF status. Although
the response rate is only 15–20 per cent, in those patients
who do show a response this can be sustained for some
considerable time. There are hopes that some patients
may have even been cured but follow-up has generally
not been long enough to establish this.
There is much interest in metastatic melanoma at
present, with numerous trials underway, especially in
combining targeted therapies where by blocking two dif-
ferent steps in the same pathway a much greater melan-
oma cell kill may result. Another drug which blocks a
specific pathway target is trametinib which is a MEK
inhibitor. When combined with dabrafenib, there is
both a progression free survival benefit and an overall
S139
survival benefit. Another MEK inhibitor cobimetinib,
shows benefit when given with vemurafenib, when com-
pared with giving vemurafenib alone.
Nivolamab is also a novel agent. It is a programmed
death 1 (PD-1) checkpoint inhibitor which also shows
complimentary benefit in metastatic melanoma when
given together with ipilimumab, compared with each
drug alone and this is now proposed as a standard of
care in those patients who have wild-type BRAF, i.e.
not showing a BRAF mutation. If this regimen does
become standard of care it may not remain so for
very long as the field is advancing so quickly.
For patients who become refractory to ipilimumab,
and to the BRAF and MEK inhibitors there is a further
new agent pembrolizumab, which targets the PD-1
receptor, and can extend progression-free survival.
Palliative RT is often used in metastatic disease
(stages IV, M1a–c). Radiotherapy dose fractionation
is non-standard in most of these treatments. Commonly
used regimens include 8 Gy single fraction, 20 Gy in
five fractions, 30 Gy in six fractions (alternate days),
the latter fractionation being used most commonly for
all brain RT for brain metastasis, and a host of local
variations in different RT departments. There is no
accepted role for the use of concomitant chemotherapy
(although temozolomide has been tested with RT in
cerebral metastases). There is emerging evidence that
SRS can be beneficial in those patients who have a
small number of brain metastases, usually less than
three, where very focused high-dose RT can be given
to the metastases, with very little dose to the surround-
ing brain.
Recommendations
• All patients with cutaneous melanoma should
have their original tumour checked for BRAF
status, and their subsequent targeted
biological therapy based on this (R)
• Patients who develop brain metastases should
be considered for stereotactic radiosurgery
(R)
Mucosal melanoma (upper aerodigestive
tract)
Introduction
Mucosal melanoma of the upper aerodigestive tract is a
rare malignancy with a poor prognosis. Management
recommendations are based upon retrospective case
series, few of which exceed 100 patients. Mucosal mel-
anoma accounts for less than 1 per cent of all melano-
mas, and less than 10 per cent of all head and neck
melanomas. The median age of patient presentation is
the sixth decade, but case reports span the age range.
The function of melanocytes in mucosa is uncertain.
The most common sites of head and neck mucosal mel-
anoma are the nasal and oral cavities. Pharyngeal,
S140 O A AHMED, C KELLY

laryngeal and oesophageal melanomas are exceedingly skull base extension from sinonasal melanoma is asso-
rare. Melanocytes in the nasal cavity can be found in ciated with poor survival and is seldom justified.
the respiratory epithelium, nasal glands, nasal septum, Radical surgical excision involving severe functional
and the middle and inferior turbinates. In oral mucosa, deficits should not be performed in the context of estab-
melanocytes are located along the tips and peripheries lished metastatic disease.
of the rete pegs. Unlike cutaneous melanoma, no risk Reports indicate high rates of local recurrence (31–85
factors for the development of this disease have been per cent), regional recurrence, and distant metastasis
identified, though cigarette smoke and other air pollu- (25–50 per cent) as well as poor five-year survival
tants may play a role. It is thought that a preceding atyp- rates (13–48 per cent), and a median survival of less
ical melanocytic hyperplasia occurs in a significant than two years, for head and neck mucosal melanoma.
proportion. The predominant mode of treatment failure is local
recurrence, and this usually occurs within a year of
Clinical presentation initial treatment. It is frequently accompanied by the
Sinonasal melanoma presents in the same way as other appearance of regional and distant metastases. Distant
sinonasal malignancies and is primarily influenced by metastasis is associated with short survival time.
site of origin. Nasal obstruction, followed by discharge While the view of mucosal melanoma as a ‘radio-
and bleeding, predominates. The commonest site is the resistant’ tumour has been challenged, the role of
anterior portion of the nasal septum. Oral mucosal mel- post-operative RT remains unclear. Its use has been
anoma most often presents as a painless mass, which reported to improve local control. Short-course,
may or may not be pigmented. Ulceration and bleeding hypofractionated schedules (e.g. 30 Gy in six frac-
are also common. The majority occur on the alveolar tions over two weeks, 50 Gy in 20 fractions), to rela-
gingiva and palate. tively small volumes, compared with other head and
neck practice are frequently employed. Adjuvant
Assessment and staging chemotherapy and biological therapeutic strategies
Endoscopic assessment and imaging, as appropriate to have been employed with encouraging response
the primary site, is necessary, following which staging rates. For metastatic disease, unfortunately only a
is performed (Table V). tiny percentage of mucosal melanomas show a
BRAF mutation; therefore it is usually not appropri-
Management ate to use BRAF inhibitors, so chemotherapy in the
form of biological agents has to depend on immuno-
The prevailing opinion is that localised disease is best therapy with ipilimumab24 or the newer agents such
managed with primary surgery which aims to achieve as pembrolizumab, although to date there has been
clear surgical margins.9 Craniofacial resection for no specific study of the latter agent’s efficacy specif-
ically in mucosal melanoma.
TABLE V
TNM STAGING SYSTEM FOR MUCOSAL MELANOMAS Key points
I–Primary tumour • Cutaneous melanoma is the fifth commonest
cancer in the UK; the incidence of melanoma
TX Primary tumour cannot be assessed doubled in the three decades following 1970
T3 Epithelium and/or submucosa (mucosal
disease) • Despite widely used checklists, the clinical diag-
T4a Deep soft tissue, cartilage, bone, overlying nosis of melanoma can be difficult and a biopsy
skin is needed for diagnosis
T4b Brain, dura, skull base, lower cranial
nerves (IX, X, XI, XII), masticator • The thickness of cutaneous melanoma greatly
space, carotid artery, prevertebral space, influences both its treatment and its prognosis
mediastinal structures • Staging includes microstaging of the primary mel-
N–Regional lymph nodes anoma and clinical/radiological evaluation for
NX Regional lymph nodes cannot be assessed metastases
N0 No regional lymph node metastasis • Mucosal melanoma is a poor prognostic disease
N1 Regional lymph node metastasis
• Wide local excision, with appropriate margins
M–Distant metastasis based on the thickness of the tumour, with or
M0 No distant metastasis without lymph node dissection of the involved
M1 Distant metastasis
nodal basins, is the mainstay of treatment for
Stage grouping: primary cutaneous melanoma
Stage III T3 N0 M0 • Excision of localised mucosal melanoma with
Stage IVA T3 N1 M0
T4a N1 M0 clear margins is the mainstay of treatment, but
Stage IVB T4b Any N M0 radical excision with functional compromise has
Stage IVC Any T Any N M1 not shown oncological benefits. Advances in
Note: Mucosal melanomas are aggressive tumours, therefore T1 immunotherapy have revolutionised the manage-
and T2 are omitted as are stages I and II ment of distant metastases
HEAD AND NECK MELANOMA: UK GUIDELINES
Acknowledgements
The authors acknowledge the contributions of Jeremy
McMahon, Taimur Shoaib, Kevin Harrington,
Andrew S. Jones and Aamir Memon to the previous
edition of this manuscript.
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Address for correspondence:
Omar A Ahmed,
Department of Plastic and Reconstructive Surgery,
The Newcastle upon Tyne Hospitals NHS Trust,
Newcastle upon Tyne, UK
E-mail: omar.ahmed@nuth.nhs.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S142–S149. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000566

Management of Salivary Gland Tumours: United

Kingdom National Multidisciplinary Guidelines

S SOOD1, M MCGURK2, F VAZ3

1
Department of Otolaryngology – Head and Neck Surgery, Bradford Teaching Hospitals, Bradford, 2Department
of Oral and Maxillofacial Surgery, Guy’s Hospital, London, and 3Department of Head and Neck Surgery,
University College London Hospital, London, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. Salivary gland tumours are rare and have very wide histological heterogeneity, thus making
it difficult to generate high level evidence. This paper provides recommendations on the assessment and
management of patients with cancer originating from the salivary glands in the head and neck.

Recommendations
• Ultrasound guided fine needle aspiration cytology is recommended for all salivary tumours and cytology
should be reported by an expert histopathologist. (R)
• Adjuvant radiotherapy (RT) following surgery is recommended for all malignant submandibular tumours
except in cases of small, low-grade tumours that have been completely excised. (R)
• For benign parotid tumours complete excision of the tumour should be performed and offers good cure
rates. (R)
• In the event of intra-operative tumour spillage, most cases need long-term follow-up for clinical observation
only. These should be raised in the multidisciplinary team to discuss the merits of adjuvant RT. (G)
• As a general principle, if the facial nerve function is normal pre-operatively then every attempt to preserve facial
nerve function should be made during parotidectomy and if the facial nerve is divided intra-operatively then
immediate microsurgical repair (with an interposition nerve graft if required) should be considered. (G)
• Neck dissection is recommended in all cases of malignant parotid tumours except for low-grade small
tumours. (R)
• Where malignant parotid tumours lie in close proximity to the facial nerve there should be a low threshold for
adjuvant RT. (G)
• Adjuvant RT should be considered in high grade or large tumours or in cases where there is incomplete or close
resection margin. (R)
• Adjuvant RT should be prescribed on the basis of clinical factors in addition to histology and grade, e.g. stage,
pre-operative facial weakness, positive margins, peri-neural invasion and extracapsular spread. (R)

Introduction surgeon that also presents challenges from a manage-

Salivary gland malignancies are rare and the under-
standing of this disease is mostly based on clinical
series rather than randomised evidence which is unlike-
ly to emerge for these tumours. Approximately 300
cases are registered each year in England and Wales
of which fewer than 10 occur in children (under 19
years of age).1 Population-based studies report that in
a population of one million, eight to nine malignant sal-
ivary gland tumours can be expected per annum.
Interspersed with this, malignant salivary gland
disease is a larger workload of benign tumours, often
performed by the non-head and neck oncological
ment perspective.
Although, overall, tumours are more common in the
parotid, the incidence of malignancy is higher in the
submandibular and minor salivary glands.2 Salivary
tumours are uncommon in children, but a greater pro-
portion (20–30 per cent) of them are malignant
(usually low-grade mucoepidermoid carcinomas).
Salivary gland tumours present a diverse range of
histological and clinical behaviours. The rarity of
these tumours combined with the diverse histology
means that there is a lack of studies that can be used
to provide strong recommendations for each individual
SALIVARY GLAND TUMOURS: UK GUIDELINES S143

TABLE 1 Carcinomas are often further classified as high

WHO CLASSIFICATION OF SALIVARY GLAND grade, low grade or mixed, the latter inferring a vari-
TUMOURS 20053 able behaviour depending on the histological picture.
Malignant epithelial tumours Except in the case of mucoepidermoid tumours, the
Acinic cell carcinoma clinicopathological correlation has proved unreliable.
Mucoepidermoid carcinoma It should be recognised that the clinical behaviour
Adenoid cystic carcinoma
Polymorphous low-grade adenocarcinoma rather than the histology of a tumour provides a better
Epithelial myoepithelial carcinoma treatment guide and it is important to consider clinical
Clear cell carcinoma, not otherwise specified factors in addition to histology and grade when plan-
Basal cell adenocarcinoma
Sebaceous carcinoma ning treatment.4
Sebaceous lymphadenocarcinoma
Cystadenocarcinoma
Low-grade cribriform cystadenocarcinoma Clinical presentation
Mucinous adenocarcinoma In general, salivary tumours are present in two forms: a
Oncocytic carcinoma
Salivary duct carcinoma simple palpable lump (well-defined, discrete and
Squamous cell carcinoma mobile) or a lump with significant accompanying
Undifferentiated carcinoma symptoms (pain, rapid growth, fixity to surrounding
Small cell carcinoma
Large cell carcinoma structures, nerve involvement or neck metastasis).
Lymphoepithelial carcinoma The latter features are all suggestive of malignancy.
Adenocarcinoma, not otherwise specified Both should be seen in a rapid access neck lump
Carcinoma ex pleomorphic adenoma malignant mixed
tumour clinic ideally to have the appropriate assessments and
Myoepithelial carcinoma management plans formulated.
Soft tissue tumours
Haemangioma
Haematolymphoid tumours Assessment and staging
Hodgkin lymphoma
Metastasising pleomorphic adenoma A third of malignant tumours have an indolent nature
Diffuse large B-cell lymphoma and may be clinically indistinguishable from benign
Extranodal marginal zone B cell lymphoma lesions. Open biopsy is not encouraged in apparently
Secondary tumours
Soft tissue benign lesions as it carries a theoretical risk of
Haematopoetic seeding, but it sometimes has a role in the frankly
Benign epithelial tumours malignant lesion (open or core biopsy) especially
Pleomorphic adenoma
Myoepithelioma when radical surgery is being contemplated. As indo-
Basal cell adenoma lent lesions may masquerade as benign lumps the
Warthin’s tumour (adenolymphoma) definitive histology sometimes may not be available
Oncocytoma
Cystadenoma until after surgical resection. Diagnosis and manage-
Papillary cystadenoma ment of these tumours is therefore based on the clin-
Mucinous cystadenoma ical presentation, imaging and cytology and/or
Keratocystoma
Canalicular adenoma histology results.
Sialadenoma papilliferum
Sebaceous adenoma
Sialoblastoma Fine needle aspiration cytology (FNAC) and
Lymphadenoma core biopsy
Benign papilloma (intraductal/inverted ductal/ductal)
This is the primary diagnostic tool for salivary gland
WHO = World Health Organization lesions (parotid, submandibular and minor salivary),
and has additional value if examined by a cytopatholo-
gist or pathologist experienced in the diagnosis of
salivary gland disease. This can distinguish malignant
histologic subtype of salivary tumour. The World
from benign disease in 90 per cent of cases.5
Health Organization (WHO) classification has been
However, it is essential to ensure that fine needle aspir-
modified on a number of occasions, the last being in
ation results are interpreted in the context of all clinical
2005.3 A list of the more common adenomas and
information.
carcinomas is given in Table 1. Each histologic
subtype is supposedly a unique entity in itself, but
this notion has to be accepted with caution. Salivary Imaging considerations
gland neoplasms are generally slow growing lesions Ultrasound by a skilled head and neck radiologist is an
and patients have to be followed up for 10 years or essential tool as part of initial assessment and provides
more before one is confident of the natural history of excellent information about the primary tumour as well
the histological entity. In most instances, this informa- as cervical lymph node status.6 It can be combined with
tion is not available. At present the unique clinical FNAC and in experienced hands, helps distinguish
behaviour of many of the new subtypes is still to be benign from malignant lesions in about 80 per cent of
identified. cases.
S144
Recommendation
• Ultrasound guided FNAC is recommended
for all salivary tumours and cytology should
be reported by an expert histopathologist (R)
Non-homogeneous, muscle infiltration or suspicious
regional lymph node appearances on cross-sectional
imaging (computed tomography (CT) or magnetic res-
onance imaging (MRI)) are suggestive of malignancy.
However, its main role is to determine size, position
and relationship to adjacent structures. Computed tom-
ography imaging is useful in proven malignancy to
exclude distant metastases which carry a poor
prognosis.
Open biopsy
This should be avoided in major salivary gland lesions
due to a risk of spillage unless the lesion appears
frankly malignant and no cytological diagnosis has
been made. In this instance, histological confirmation
may inform planning of a more radical surgical
approach. Histology may still be obtained by the use
of ultrasound guided core biopsy specimens rather
than an open biopsy. For minor salivary glands, open
biopsy is permissible, but where possible should be
undertaken by a dermatological punch.
Frozen section
Accurate diagnosis is often difficult and false negative
rates are significant therefore it is essential that if
frozen section is being considered it must be done by
an expert pathologist.7 On some occasions pre-opera-
tive cytology and/or histology may remain unclear
and therefore the frozen section may have a role in
parotid surgery. It is important not to breach the
tumour capsule during parotid surgery and a partial par-
otidectomy specimen should be sent for the frozen
section which may help determine the presence of
malignancy and therefore help inform a decision
regarding proceeding to radical surgery. This may be
preferred rather than waiting for results of a partial par-
otidectomy as completion parotidectomy at a later stage
carries a significant morbidity, especially with regards
to facial nerve function.
Staging
The Tumour–Node–Metastases (7) system staging for
salivary gland primary tumour is shown in Table II.
The staging of metastatic neck nodes for salivary
gland cancer is similar to that for other metastatic disease.
Management
Submandibular gland
Benign tumours. The submandibular gland should be
excised in a supracapsular plane. A wide dissection
of local tissues is not required.
S SOOD, M MCGURK, F VAZ
TABLE II
T-STAGING FOR SALIVARY GLAND TUMOURS
Tx Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Tumour ≤2 cm in greatest dimension without
extraparenchymal extension∗
T2 Tumour >2 cm but ≤4 cm in greatest dimension without
extraparenchymal extension∗
T3 Tumour >4 cm and/or tumour having extraparenchymal
extension∗
T4a Tumour invades skin, mandible, ear canal and/or facial
nerve
T4b Tumour invades skull base and/or pterygoid plates and/or
encases carotid artery
∗
Extraparenchymal extension is clinical or macroscopic evidence
of invasion of soft tissues. Microscopic evidence alone does not
constitute extraparenchymal extension for classification purposes.
Malignant tumours. Historical survival rates in subman-
dibular gland cancer are lower than those achieved in
parotid or minor salivary gland malignancy.8,9 This
has been attributed to the absence of a pre-treatment
malignant diagnosis and therefore performance of con-
servative resection. It is important that if a neoplasm is
suspected or a firm supposedly fibrotic submandibular
gland encountered then every effort should be made to
establish whether it is benign or malignant prior to
surgery.
Surgical management of the primary tumour. Wide
excision is appropriate for tumours confined to the
gland combined with some form of neck dissection.
Some argue in favour of a wider resection for
adenoid cystic tumours but even with radical surgery,
it is frequently difficult to obtain adequate surgical
margins.10 The advice for radical surgery in subman-
dibular malignancy is at variance with recommenda-
tions for the preservation of the uninvolved facial
nerve in parotid disease. Clinically high-grade
tumours should be treated aggressively with excision
of the gland plus a 2 cm margin of apparently healthy
tissue. Resection of involved nerves with microscopic
negative margins is desirable. Large infiltrative
tumours with bony involvement are treated with com-
posite resection of tumour, adjacent soft tissue cuff
and bony resection as appropriate.
Surgical management of the neck metastases. In the
N0 neck, patients should undergo clearance of nodes
with a selective neck dissection (levels 1 and 2A).
Clinically high-grade tumours or tumours with suspi-
cious MRI appearances should have an elective select-
ive dissection (levels 1–3).
The following histological types have higher risk of
metastasis: high-grade mucoepidermoid carcinoma,
squamous cell carcinoma (SCC), anaplastic tumours
and carcinoma ex pleomorphic adenoma. Carcinoma
ex pleomorphic adenoma has been redefined and
some types act as benign tumours.11 It is the frankly
malignant variety that carries the risk of metastases.
Patients with clinically confirmed neck metastasis
SALIVARY GLAND TUMOURS: UK GUIDELINES
(N+) should have a neck dissection, the extent of
which will be based on disease stage and location.
Primary radiotherapy (RT). Primary RT may be
applicable in inoperable tumours where palliation can
be achieved.12 The role of heavy ions such as proton
and carbon ion therapy is being explored and is as
yet unresolved.
Post-operative RT. ‘The 4 cm rule’: survival is sig-
nificantly worse in tumours greater than 4 cm in diam-
eter.12 With increasing size the risk of occult metastasis
is greater and tumour size is a major determinant of
distant metastasis. Tumours greater than 4 cm in size
fall into the class of high risk or complex tumours,
and adjuvant RT is advised. Post-operative RT should
be commenced within six weeks of surgery.
Indications for post-operative RT:
• High-grade or advanced stage tumours (>4 cm)
with a high risk of local recurrence
• Residual neck disease or microscopic extracapsu-
lar spread from lymph nodes
• Following surgery for recurrent disease
• Adenoid cystic carcinomas (ACC).
Surveillance. Following surgery alone or surgery
followed by RT careful surveillance is required.
Ultrasound offers an accurate method of detecting
recurrence but a baseline MRI three months following
treatment is useful for comparison.
Recommendation
• Adjuvant RT following surgery is
recommended for all malignant
submandibular tumours except in cases of
small, low-grade tumours that have been
completely excised (R)
Parotid gland
Benign tumours. Traditional management of benign
parotid tumours is by dissection of the facial nerve
leading to a superficial or total parotidectomy. There
is currently no agreement in the literature as to the
extent of resection to obtain an adequate margin in
benign tumours.13 There is increasing recognition that
operations less than the traditional procedures (extra-
capsular dissection, partial parotidectomy and even
endoscopically assisted parotidectomy) are as effective
in selected patients.14 It is preferable that these proce-
dures should be performed by expert surgeons in
appropriately selected cases, such as small tumours
confined to the superficial lobe. A ‘lumpectomy’ pro-
cedure should not be done due to high recurrence
rates. As the facial nerve not infrequently is very
close to the tumour (especially in larger tumours)
careful dissection avoiding tumour rupture is
S145
important. Tumour spillage carries an increase in the
rate of recurrence over a prolonged period and therefore
long-term follow-up is recommended in such cases.15
Adjuvant RT for such cases should be discussed in a
multidisciplinary team (MDT) setting, but the use of
RT in these cases is controversial and is generally not
recommended especially in younger patients due to
the risk of radiation-induced tumours.
Recurrent benign parotid tumours. These will usually be
treated surgically. Careful pre-operative ultrasound
marking may be helpful. A widefield removal of
tissue in the parotid bed with preservation of the
facial nerve is recommended. The patient should be
discussed in the MDT for the suitability of post-opera-
tive RT to reduce re-recurrence.
Recommendations
• For benign parotid tumours complete excision
of the tumour should be performed and offers
good cure rates (R)
• In the event of intra-operative tumour
spillage, most cases need long-term follow-up
for clinical observation only. These should be
discussed in the MDT to discuss the merits of
adjuvant RT (G)
Malignant tumours
Surgical management of the primary tumour. In
carcinoma, surgery is the treatment of choice with
management tailored to the individual case.16 A con-
servative parotidectomy should be performed with
preservation of the functioning facial nerve providing
there is no tumour invasion. For small, low-grade
superficial tumours a partial parotidectomy (superficial
parotidectomy or wide local resection with an adequate
margin of at least 1.5 cm) may suffice but otherwise a
total conservative parotidectomy is advocated with
resection of adjacent structures if necessary to
achieve an en-bloc resection. Any part of the facial
nerve not infiltrated by tumour should be preserved
and a frozen section may be needed to determine
nerve involvement. If the facial nerve is functional
pre-operatively, then primary nerve grafting should be
performed following radical resection. Adenoid cystic
carcinoma characteristically has a diffuse pattern of
spread and incomplete surgical clearance is the norm.
A total parotidectomy with sacrifice of any part of
any of the nerves overtly involved in tumour is
desirable.
Management of the facial nerve in the context of
parotid tumours. The facial nerve can be damaged as
a sequelae of parotid surgery, either as a planned
event when removing a malignant tumour or inadvert-
ently. The damage can be a division of the nerve or can
occur with the nerve intact, i.e. a neuropraxia. If the
S146
nerve is divided, it should be repaired as soon as pos-
sible, ideally acutely. Direct microsurgical repair
without tension, or repair utilising a nerve graft, offer
the best chance of a good recovery. A delay of more
than a year in nerve repair has been shown to be an
adverse factor in patient recovery. If a proximal nerve
stump is not available or significant amounts of facial
muscle have been removed, facial re-animation will
require importation of a new muscle and nerve
supply. The facial nerve can routinely be found and
exposed in the mastoid segment of the temporal bone
if the nerve cannot be found in the neck. Re-animation
techniques can be one stage using either microsurgical
importation of a free muscle transfer, or regional
involving a temporalis myoplasty. Such techniques
require substantial expertise and patients with signifi-
cant facial paralysis should be referred to a service
which can offer a full spectrum of reconstructive
options regarding facial re-animation, including care
of the eye.
Recommendation
• As a general principle, if the facial nerve
function is normal pre-operatively then every
attempt to preserve facial nerve function
should be made during parotidectomy and if
the facial nerve is divided intra-operatively
then immediate microsurgical repair (with an
interposition nerve graft if required) should
be considered (G)
Surgical management of the neck metastases. The lit-
erature reports rates between 13 and 39 per cent of
pathological neck node metastases in parotid cancer.
Neck dissection should be performed in patients with
clinical or radiological evidence of nodal disease.17
A prophylactic selective neck dissection should be
considered for patients with high-stage and/or clinical-
ly high-grade tumours (i.e. adenocarcinoma, squamous
and undifferentiated carcinomas, high-grade mucoepi-
dermoid carcinoma and carcinoma ex pleomorphic
adenoma).18,19 In addition, neck dissection provides a
histological specimen which provides important prog-
nostic information such as extracapsular spread which
has been shown to be a poor prognostic indicator.
Recommendation
• Neck dissection is recommended in all cases of
malignant parotid tumours except for low-
grade small tumours (R)
Radiotherapy. Radiotherapy is effective in reducing
the risk of recurrent benign tumours. It has application
in high risk of recurrence pleomorphic adenoma cases,
S SOOD, M MCGURK, F VAZ
namely gross wound contamination and as an adjuvant
therapy for treatment of multinodular recurrent
disease.15
Adjuvant RT is appropriate for large tumours
(>4 cm), recurrent disease, patients with incomplete
or close margins, peri-neural invasion, extension
beyond the gland, nodal disease, in metastatic disease
and is increasingly the norm following treatment of
ACC and high-grade tumours.12
Recommendations
• Where malignant parotid tumours lie in close
proximity to the facial nerve there should be a
low threshold for adjuvant RT (G)
• Adjuvant radiation should be considered in
high-grade or large tumours or in cases
where there is incomplete or close resection
margin (R)
• Adjuvant radiation should be prescribed on
the basis of clinical factors in addition to
histology and grade, e.g. stage, pre-operative
facial weakness, positive margins, peri-neural
invasion and extracapsular spread (R)
Recurrent cancer. This requires careful evaluation of the
patient with repeat imaging and a review of the hist-
ology from the initial excision. It will usually require
more radical surgery with sacrifice of the facial nerve
and overlying skin if there is suspicion of involvement
by tumour. Super-radical resections of the skull base
have not to date shown convincing evidence of
improved survival. Consider chemotherapy and/or
RT for palliation.
Minor salivary glands
The natural history of intra-oral minor salivary gland
tumours is similar to the parotid and submandibular
glands. Outcome is worse for ‘hidden sites’, i.e larynx,
nasopharynx and nose. The prognosis for these patients
as with parotid and submandibular glands is related to
stage of disease rather than the histology.
Benign tumours. Tumours of the palate can be safely
resected at the subperiosteal level without removing
palatal bone. Proven benign tumours in soft tissue
can be removed by careful local dissection.
Malignant tumours
Surgical management of the primary tumour. Most
cases are treated in a similar way to SCC, with en-bloc
resection with depth of excision compatible with treat-
ment of SCC to ensure adequate resection margins.20
Significant defects are repaired as appropriate.
Surgical management of the neck metastases.
Therapeutic neck dissection is indicated for lymph
node involvement. Elective neck dissection is indicated
SALIVARY GLAND TUMOURS: UK GUIDELINES
for high-stage and clinically high-grade disease such as
high-grade adenocarcinoma, invasive carcinoma ex
pleomorphic adenoma, SCC, high-grade mucoepider-
moid and undifferentiated carcinoma.18
Radiotherapy. The following factors are indications
for post-operative RT12:
• Microscopic residual disease
• Adenoid cystic tumours
• Aggressive undifferentiated tumours
• A‘4 cm rule’.
Natural history and management principles
for common salivary malignancies
Acinic cell carcinomas
These tumours account for about 3 per cent of parotid
tumours, where they occur most commonly. Peak inci-
dence is in the fifth decade. Other features include:
• A variable histological pattern, multifocal origin
and occasionally bilateral location
• Determinate survival rates of 90 per cent at five
years and 55 per cent at 20 years9
• Lymph node metastatic rate of approximately
10 per cent.
Most acinic cell cancers are low grade (approximate-
ly 80 per cent). Small indolent peripheral lesions can be
managed by less than a total parotidectomy. In low-
grade acinic cell cancers, adjuvant RT following com-
plete excision may not confer survival benefit and
therefore the role of adjuvant RT should be considered
carefully in such cases.21 Total parotidectomy with
preservation of uninvolved nerves is recommended.
Elective neck dissection is usually not indicated.
Mucoepidermoid tumour
These tumours have variable malignant potential with
low-grade lesions following an indolent course.
Histologically high-grade lesions have a natural
history similar to SCC. The histological grade corre-
lates with several prognostic factors including presence
of lymphatic spread and survival.9,22 The key features
are detailed below:
• Most common major salivary gland tumour (4–9
per cent) with over 90 per cent occurring in the
parotid but overall more frequent in minor salivary
glands
• Most common malignant salivary gland tumour in
children and usually presents in its indolent form
• Highest incidence third to fifth decade with no dif-
ference in gender incidence
• In the parotid, it is almost always in the superficial
lobe
• Histological division into low, intermediate and
high-grade correlates with prognosis, although
S147
‘low-grade’ tumours can on occasion be
aggressive22
• Five-year survival varies between 86 per cent for
low-grade and 22 per cent for high-grade
tumours. Peri-neural and lymphovascular invasion
is not uncommon in these tumours
• Incidence of lymph node metastases is 40 per cent
in intermediate and high-grade tumours
• Small low-grade tumours can be removed by less
than a total parotidectomy and bigger ones
(>2 cm) will frequently be in close contact with
the facial nerve and the aforementioned advice
pertains regarding adjuvant RT
• Adjuvant RT indicated for high-grade tumours.
Recommendation
• In cases of mucoepidermoid carcinoma, the
histologic grade is an important factor
correlating to outcome and should be
considered when planning treatment (G)
Adenoid cystic carcinoma
This is the most common salivary gland malignancy
(20–25 per cent of all malignant salivary gland neo-
plasms), occurs at mucosal sites more frequently than
in major salivary glands, and accounts for 2–6 per
cent of parotid tumours and approximately 15 per
cent of submandibular tumours. It is characterised by:
• Slow, pervasive growth and a high incidence of
peri-neural infiltration. Relapsing neuralgic type
pain can be a feature of early hidden disease.
Patients can be ‘labelled’ as having atypical
facial pain with consequent diagnostic delay
• Variable histologic appearance but difficult to cor-
relate with clinical behaviour although some
report cribriform pattern to have better prognosis
than tubular or solid pattern tumours.
Treatment should involve wide local excision with
preservation of uninvolved major nerves. Adjuvant
post-operative RT is often indicated.10 Stage I and II
cancers can be cured although the survival curve
never flattens even after 20 years. Patient with stage
III and IV diseases have a poor prognosis with low
survival rates at 10 years. Slow growth rate makes
five-year survival rates unreliable marker of cure.
Only 20 per cent of patients with pulmonary metastases
survive more than five years.
Adenocarcinoma
This uncommon tumour is most frequently (90 per
cent) found in the parotid gland. It is characterised by:
• Equivalent gender incidence, affecting any age
and is one of the commonest tumours seen in
children
S148
• Histologic appearances varying between low-
grade well-differentiated papillary or mucinous
patterns to high-grade, undifferentiated lesions
• Distant metastatic incidence rates of 40 per cent
for high-grade tumours, directly related to survival
rates
• A 75 and 19 per cent five-year survival for low-
grade and high-grade tumours, respectively.
Treatment is by wide local resection with elective
neck dissection and adjuvant RT for clinically high-
grade tumours.
Malignant mixed tumour (carcinoma ex pleomorphic
adenoma)
Carcinoma ex pleomorphic adenoma is a broad cat-
egory of carcinomas of the salivary glands.11 The
name is probably a misnomer for only a minority of
malignant mixed tumours arise from pleomorphic
adenomata. These are typically tumours with a
history of multiple recurrences with surgery and RT.
The remainder are probably not a homogeneous
group of tumours and may occur de novo rather than
following a malignant generation of pleomorphic
adenoma. The frequency varies between 2 and
5 per cent.
Different patterns of malignant change can occur in
pleomorphic adenoma of which the most commonly
encountered is carcinoma ex pleomorphic adenoma,
the other types being a true malignant mixed tumour
and metastasising pleomorphic adenoma.
The tumours are classed as in situ carcinoma, non-
invasive (intra-capsular including in situ carcinoma)
minimally invasive (<1.5 mm) and invasive.11 The
clinical behaviour of early or minimally invasive
tumours is similar to that of pleomorphic salivary
adenoma. Clinical malignant behaviour is associated
with only the malignant foci that extend beyond the
capsule of the tumour and these tumours tend to be
high grade with a high incidence of haematogenous
metastasis. Cure rates at 5, 10 and 15 years are 40, 24
and 19 per cent, respectively.
Squamous cell carcinoma
This rare primary tumour is often mistaken for either a
high-grade mucoepidermoid lesion or metastasis from
another primary site; however, it is commonly metasta-
ses from a skin cancer. Features of this cancer include:
• Male to female incidence ratio 2:1
• Tendency to occur in the elderly (seventh decade)
• Metastatic disease presents initially as a discrete
lump in the parotid however unlike salivary neo-
plasms SCC has a propensity for early extracapsu-
lar extension. In the parotid, this threatens local
structures and prompt surgical intervention
should be the rule. A few weeks’ delay can
make a significant difference to the complexity
of surgery
S SOOD, M MCGURK, F VAZ
• A poor prognosis and should be treated as high-
grade mucoepidermoid lesions.
Radical resection with adjuvant RT offers the best
form of management.
Key points
• There is a limited amount of clinical evidence for
the management of salivary gland tumours
• Salivary gland tumours exhibit a diverse range of
histological type and clinical behaviour
• Salivary gland malignancies are rare
• Investigations are essential to help tailor appropri-
ate treatment and should include an FNA reported
by an expert pathologist
• The majority of tumours will be treated by
surgery, the extent of which should be tailored
to the size, clinical and histological type of tumour
• As a general principle in cases where there is
normal facial nerve function then the facial nerve
should be preserved during surgical treatment
• Adjuvant radiotherapy should be considered in
malignant cases with adverse clinical or histo-
logical features
• Elective treatment of the neck will be required in
the majority of malignant tumours.
References
1 Bradley P. General epidemiology and statistics in a defined UK
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the Management of Salivary Gland Disease. Oxford
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3 Barnes L, Eveson J, Reichart P, Sidransky D. Pathology and
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1278–82
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EW. Carcinoma of major salivary glands. Recent trends. Arch
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Carcinoma of the parotid and submandibular glands – a study
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10 Garden AS, Weber RS, Morrison WH, Ang KK, Peters LJ. The
influence of positive margins and nerve invasion in adenoid
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11 Di Palma S. Carcinoma ex pleomorphic adenoma, with parti-
cular emphasis on early lesions. Head Neck Pathol 2013;
7(Suppl 1):S68–76
12 Terhaard CH, Lubsen H, Rasch CR, Levendag PC, Kaanders
HH, Tjho-Hislinga RE et al. The role of radiotherapy in the
treatment of malignant salivary gland tumors. Int J Radiat
Oncol Biol Phys 2005;61:103–11
13 Witt RL. The significance of the margin in parotid surgery for
pleomorphic adenoma. Laryngoscope 2002;112:2141–54
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14 Foresta E, Torroni A, Di Nardo F, de Waure C, Poscia A,
Gasporini G et al. Pleomorphic adenoma and benign parotid
tumors: extracapsular dissection vs superficial parotidectomy
– review of literature and meta-analysis. Oral Surg Oral Med
Oral Pathol Oral Radiol 2014;117:663–76
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Relationship between histopathology of pleomorphic adenoma
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omy. J Surg Oncol 2012;106:942–6
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gland. Analysis of treatment results and patterns of failure after
combined surgery and radiation therapy. Cancer 1993;71:
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Lichius O. Patterns of lymph node spread and its influence on
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34:932–7
18 Armstrong JG, Harrison LB, Thaler HT, Frieldander-Klar H,
Fass DE, Zelefsky MJ et al. The indications for elective treat-
ment of the neck in cancer of the major salivary glands.
Cancer 1992;69:615–9
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Otolaryngol 2010;130:286–92
20 Parsons JT, Mendenhall WM, Stringer SP, Cassisi NJ, Million
RR. Management of minor salivary gland carcinomas. Int J
Radiat Oncol Biol Phys 1996;35:443–54
21 Andreoli MT, Andreoli SM, Shrime MG, Devaiah AK.
Radiotherapy in parotid acinic cell carcinoma: does it have an
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Address for correspondence:
Sanjai Sood,
Department of Otolaryngology – Head and Neck Surgery,
Bradford Teaching Hospitals,
Bradford, UK
E-mail: sanjsood@aol.com
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S150–S160. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000578

Management of thyroid cancer: United Kingdom

National Multidisciplinary Guidelines

A L MITCHELL1, A GANDHI2, D SCOTT-COOMBES3, P PERROS1

1
The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, 2Department of Breast and
Endocrine Surgery, University Hospital of South Manchester, Manchester, and 3University Hospital of Wales,
Cardiff, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. This paper provides recommendations on the management of thyroid cancer in adults and is
based on the 2014 British Thyroid Association guidelines.

Recommendations
• Ultrasound scanning (USS) of the nodule or goitre is a crucial investigation in guiding the need for fine needle
aspiration cytology (FNAC). (R)
• FNAC should be considered for all nodules with suspicious ultrasound features (U3–U5). If a nodule is smaller
than 10 mm in diameter, USS guided FNAC is not recommended unless clinically suspicious lymph nodes on
USS are also present. (R)
• Cytological analysis and categorisation should be reported according to the current British Thyroid Association
Guidance. (R)
• Ultrasound scanning assessment of cervical nodes should be done in FNAC-proven cancer. (R)
• Magnetic resonance imaging (MRI) or computed tomography (CT) should be done in suspected cases of
retrosternal extension, fixed tumours (local invasion with or without vocal cord paralysis) or when
haemoptysis is reported. When CT with contrast is used pre-operatively, there should be a two-month delay
between the use of iodinated contrast media and subsequent radioactive iodine (I131) therapy. (R)
• Fluoro-deoxy-glucose positron emission tomography imaging is not recommended for routine evaluation. (G)
• In patients with thyroid cancer, assessment of extrathyroidal extension and lymph node disease in the central
and lateral neck compartments should be undertaken pre-operatively by USS and cross-sectional imaging (CT
or MRI) if indicated. (R)
• For patients with Thy 3f or Thy 4 FNAC a diagnostic hemithyroidectomy is recommended. (R)
• Total thyroidectomy is recommended for patients with tumours greater than 4 cm in diameter or tumours of any
size in association with any of the following characteristics: multifocal disease, bilateral disease, extrathyroidal
spread (pT3 and pT4a), familial disease and those with clinically or radiologically involved nodes and/or
distant metastases. (R)
• Subtotal thyroidectomy should not be used in the management of thyroid cancer. (G)
• Central compartment neck dissection is not routinely recommended for patients with papillary thyroid cancer
without clinical or radiological evidence of lymph node involvement, provided they meet all of the following
criteria: classical type papillary thyroid cancer, patient less than 45 years old, unifocal tumour, less than 4 cm,
no extrathyroidal extension on ultrasound. (R)
• Patients with metastases in the lateral compartment should undergo therapeutic lateral and central compartment
neck dissection. (R)
• Patients with follicular cancer with greater than 4 cm tumours should be treated with total thyroidectomy. (R)
• I131 ablation should be carried out only in centres with appropriate facilities. (R)
• Serum thyroglobulin (Tg) should be checked in all post-operative patients with differentiated thyroid cancer
(DTC), but not sooner than six weeks after surgery. (R)
• Patients who have undergone total or near total thyroidectomy should be started on levothyroxine 2 μg per kg or
liothyronine 20 mcg tds after surgery. (R)
• The majority of patients with a tumour more than 1 cm in diameter, who have undergone total or near-total
thyroidectomy, should have I131 ablation. (R)
• A post-ablation scan should be performed 3–10 days after I131 ablation. (R)
• Post-therapy dynamic risk stratification at 9–12 months is used to guide further management. (G)
• Potentially resectable recurrent or persistent disease should be managed with surgery whenever possible. (R)
• Distant metastases and sites not amenable to surgery which are iodine avid should be treated with I131
therapy. (R)
MANAGEMENT OF THYROID CANCER: UK GUIDELINES S151

• Long-term follow-up for patients with differentiated thyroid cancer (DTC) is recommended. (G)
• Follow-up should be based on clinical examination, serum Tg and thyroid-stimulating hormone
assessments. (R)
• Patients with suspected medullary thyroid cancer (MTC) should be investigated with calcitonin and carcino-
embryonic antigen levels (CEA), 24 hour catecholamine and nor metanephrine urine estimation (or plasma
free nor metanephrine estimation), serum calcium and parathyroid hormone. (R)
• Relevant imaging studies are advisable to guide the extent of surgery. (R)
• RET (Proto-oncogene tyrosine-protein kinase receptor) proto-oncogene analysis should be performed after
surgery. (R)
• All patients with known or suspected MTC should have serum calcitonin and biochemical screening for
phaeochromocytoma pre-operatively. (R)
• All patients with proven MTC greater than 5 mm should undergo total thyroidectomy and central compartment
neck dissection. (R)
• Patients with MTC with lateral nodal involvement should undergo selective neck dissection (IIa–Vb). (R)
• Patients with MTC with central node metastases should undergo ipsilateral prophylactic lateral node dissection. (R)
• Prophylactic thyroidectomy should be offered to RET-positive family members. (R)
• All patients with proven MTC should have genetic screening. (R)
• Radiotherapy may be useful in controlling local symptoms in patients with inoperable disease. (R)
• Chemotherapy with tyrosine kinase inhibitors may help in controlling local symptoms. (R)
• For individuals with anaplastic thyroid carcinoma, initial assessment should focus on identifying the small
proportion of patients with localised disease and good performance status, which may benefit from surgical
resection and other adjuvant therapies. (G)
• The surgical intent should be gross tumour resection and not merely an attempt at debulking. (G)

Differentiated thyroid cancer
Introduction
Thyroid nodules are common, the incidence of palp-
able nodules in women and men being approximately
5 and 1 per cent, respectively. Use of ultrasound scan-
ning (USS) substantially increases their detection in the
general population to approximately 50–70 per cent.
Thyroid cancer remains rare, with an incidence in the
UK of approximately 5 per 100 000 women and 2
per 100 000 men. Thyroid cancer is the most
common endocrine malignancy, but accounts for only
1 per cent of all malignancies. Evidence suggests an
increasing incidence; however, the survival rates
remain static.
Long-term prognosis for differentiated thyroid
cancer (DTC) is excellent, with survival rates for
adults being 92–98 per cent at 10-year follow-up.
However, 5–20 per cent of patients develop local or
regional recurrence requiring further treatment and
10–15 per cent go on to develop distant metastases.
Factors influencing prognosis include gender, age at
presentation, histology and tumour stage. Accurate
diagnosis, treatment and long-term follow-up are
essential to achieve and maintain excellent survival
rates.
There have been several sets of detailed guidelines
published on the diagnosis and management of
thyroid cancer. Two key ones are the Guidelines for
the Management of Thyroid Cancer (2014) by the
British Thyroid Association and Royal College of
Physicians,1 and the Revised American Thyroid
Association Guidelines (2016).2 These documents are
extensive and cover every aspect of care in great
detail. Given differences in presentation, pathophysi-
ology and outcomes, separate guidelines exist for chil-
dren with DTC,3 and consensus statements on the
various surgical interventions.4 Patients may initially
be seen by a surgeon, endocrinologist, clinical oncolo-
gist or nuclear medicine physician, who must be a core
member of the thyroid cancer multidisciplinary team
(MDT). The goals of treatment for DTC are set out in
Box I.
BOX I
GOALS OF TREATMENT FOR DTC
• Remove the primary tumour and involved lymph
nodes
• Minimise treatment related morbidity
• Allow accurate staging of the disease
• Facilitate post-operative treatment with
radioactive iodine in appropriate patients
• Enable long-term surveillance for disease
recurrence
• Minimise the risk of disease recurrence and
distant metastases
Clinical presentation
In all cases, a detailed history is required. Clinical fea-
tures associated with an increased risk of malignancy in
individuals with a thyroid nodule include:
S152
• age younger than 20 or older than 60 years
• firmness of the nodule on palpation
• rapid growth
• fixation to adjacent structures
• vocal cord paralysis
• associated lymphadenopathy
• history of neck irradiation
• family history of thyroid cancer
• history of Hashimoto’s thyroiditis (risk factor for
thyroid lymphoma).
Symptoms warranting immediate referral. Patients pre-
senting with airway compromise, including stridor,
associated with a thyroid nodule or goitre should be
referred for an immediate opinion.
Symptoms warranting urgent general practitioner (GP)
referral (two-week wait rule). Patients presenting with
hoarseness of voice or a change in their voice asso-
ciated with a thyroid nodule or goitre, children with a
thyroid nodule, individuals with cervical lymphaden-
opathy associated with a thyroid nodule or a painless
thyroid mass, which is rapidly enlarging over a
period of weeks should be referred for an urgent
opinion.
Investigation
Recommended clinical investigations. These include:
• Clinical evaluation of thyroid, cervical and supra-
clavicular nodes
• Thyroid-stimulating hormone (TSH)
• Ultrasound of the nodule (Table I)
• Fine needle aspiration cytology (FNAC) if ultra-
sound features are suspicious of malignancy
• Documented cytological score (Table II). A core
biopsy (with or without USS guidance) is war-
ranted if a diagnosis of lymphoma is suspected
• Calcitonin only in suspected cases of medullary
thyroid cancer (MTC) (routine use not recommended)
• Pre-operative vocal cord check
• Note that a serum thyroglobulin (Tg) is not
recommended.
Ultrasound of thyroid nodules. Ultrasound is very useful
in the investigation of thyroid nodules and should be
used to guide the need for further investigation includ-
ing FNAC. Ultrasound-guided FNAC increases the
yield of diagnostic cytology significantly. Current
guidelines recommend that ultrasonographers use the
U grade (Table I) to classify nodules according to ultra-
sound appearances.5
Ultrasound evaluation of cervical lymphadenopathy.
Pathological studies suggest that microscopic lymph
node metastases are very common in papillary
thyroid cancer (PTC). However, macroscopic disease
is less common (20–50 per cent). Pre-operative
A L MITCHELL, A GANDHI, D SCOTT-COOMBES et al.
ultrasonography is effective in identifying suspicious
nodes in approximately 20–30 per cent of patients
with PTC and may alter the surgical approach. FNAC
of suspicious nodes is recommended. Tg estimation
of cystic fluid may be of use in the absence of sufficient
diagnostic material.
Recommendations
• Ultrasound scanning of the nodule or goitre is
a crucial investigation in guiding the need for
FNAC (R)
• FNAC should be considered for all nodules
with suspicious ultrasound features (U3–U5).
If a nodule is smaller than 10 mm in diameter,
USS-guided FNAC is not recommended
unless clinically suspicious lymph nodes on
USS are also present (R)
• Cytological analysis and categorisation
should be reported according to the current
British Thyroid Association Guidance (R)
• Ultrasound scanning assessment of cervical
nodes should be done in FNAC-proven
cancer (R)
• Magnetic resonance imaging (MRI) or
computed tomography (CT) should be done
in suspected cases of retrosternal extension,
fixed tumours (local invasion with or without
vocal cord paralysis) or when haemoptysis is
reported. When CT with contrast is used pre-
operatively, there should be a two-month
delay between the use of iodinated contrast
media and subsequent radioactive iodine
therapy (R)
• Fluoro-deoxy-glucose-positron emission
tomography imaging is not recommended for
routine evaluation (G)
Staging
The tumour, nodes and metastases (TNM) staging
system (Table III) is used to stage thyroid cancers
and this should be used in all cases. Post-operatively,
an ‘R’ classification can be given which indicates the
amount of residual disease present. The TNM classifi-
cation can then be used in combination with patient
characteristics to define likely prognosis (Table IV).
Surgery
Surgeons performing operations for confirmed or sus-
pected thyroid cancer should be core members of the
thyroid cancer MDT and should perform a minimum
of 20 thyroidectomies per year. Complex surgery and
lymph node surgery should be undertaken by nomi-
nated surgeons in the cancer centre with specific train-
ing in, and experience of, thyroid oncology. All
MANAGEMENT OF THYROID CANCER: UK GUIDELINES S153

TABLE I
U GRADING OF THYROID NODULES
U1 normal U2 benign U3 indeterminate/ U4 suspicious U5 malignant
equivocal

Normal thyroid Halo Homogeneous Solid Solid

tissue Iso-echoic or mildly hyper-echoic Hyper-echoic Hypo-echoic or Hypo-echoic
Cystic change ± ring down sign Solid, halo very hypo- Lobulated or irregular
Micro-cystic/spongiform (follicular lesion) echoic outline
Peripheral egg shell calcification Equivocal echogenic Disrupted Micro-calcification
Peripheral vascularity foci peripheral Globular calcification
Cystic change calcification Intra-nodular
mixed/central Lobulated vascularity
vascularity outline Shape (taller >wide)
Characteristic
associated
lymphadenopathy
No follow-up No follow-up required – routine FNAC FNAC FNAC FNAC
required not recommended, unless high level
of clinical suspicion of thyroid
cancer
FNAC = fine needle aspiration cytology

patients with suspected or confirmed thyroid cancer
should have pre-operative imaging with ultrasound.
Cross-sectional imaging with CT or MRI may also be
indicated.
In the context of thyroid cancer, surgery may be
diagnostic (e.g. hemithyroidectomy following Thy 3
or Thy 4 cytology) or therapeutic.
Thyroid surgery for papillary thyroid cancer (PTC). A
strategy for the surgical treatment of PTC is detailed
in Table V. All cases should be discussed pre-opera-
tively at the thyroid cancer MDT.
Initial surgery for follicular thyroid cancer. The majority
of patients undergoing surgery for follicular thyroid
cancer will be undiagnosed at the time of the initial
surgery (Thy 3). Frozen section histology cannot cur-
rently reliably differentiate benign follicular lesions
from follicular thyroid cancer, and therefore this strat-
egy is not recommended. An operative strategy for
surgical treatment of follicular cancer is outlined in
Table VI.
Low-risk patients with a diagnosis of minimally
invasive tumour less than 4 cm following hemithyroi-
dectomy do not require further treatment. Hurthle cell
cancers (follicular oncocytic) tend to be more aggres-
sive and should be treated by total (completion) thyroi-
dectomy (see Table VI).
Management of lymph nodes in differentiated thyroid
cancer (DTC). Prophylactic level VI lymph node dis-
section is associated with a higher incidence of recur-
rent laryngeal nerve damage and long-term
permanent hypoparathyroidism.6 It is therefore not rou-
tinely recommended, but in individuals with high-risk
tumours, this should be discussed in the spirit of perso-
nalised decision making. Prophylactic level VI nodal
dissection is not recommended in low risk, small pap-
illary and most follicular cancers.
Prophylactic level VI nodal dissection is recom-
mended in patients with known involved lateral

TABLE II
THYROID FNAC DIAGNOSTIC CATEGORIES
Thy 1 Thy 2 Thy 3 Thy 4 Thy 5
Thy 3F Thy 3A

Non- Non-neoplastic, Follicular lesion Atypia present Suspicious of thyroid Diagnostic of thyroid
diagnostic e.g. colloid cancer cancer
nodule or
thyroiditis
Repeat No follow-up if Diagnostic Repeat ultrasound and Discuss at MDT Discuss at MDT
FNAC no suspicious hemithyroidectomy∗ FNAC Diagnostic Appropriate further
US features Consider total If second Thy 3A hemithyroidectomy∗ investigations for
and no thyroidectomy in cytology obtained, staging where indicated
clinical lesions >4 cm discuss at MDT and Total thyroidectomy ±
suspicion of where incidence of consider diagnostic central node clearance
thyroid cancer malignancy is higher hemithyroidectomy∗ in appropriate high risk
patients
∗
Hemithyroidectomy consists of removal of a thyroid lobe and the isthmus
S154 A L MITCHELL, A GANDHI, D SCOTT-COOMBES et al.

TABLE III
TUMOUR, NODES AND METASTASES 7TH EDITION STAGING SYSTEM FOR DIFFERENTIATED THYROID CANCER
T stage – primary tumour
N stage – regional lymph nodes (cervical or
upper mediastinal)
M stage – distant metastases
R stage – residual disease
MDT = multidisciplinary team
TX primary tumour cannot be assessed
T0 no evidence of primary tumour
T1 tumour ≤2 cm in greatest dimension limited to the thyroid
T1a tumour ≤1 cm, limited to the thyroid
T1b tumour >1 cm but ≤2 cm in greatest dimension, limited to the thyroid
T2 tumour >2 cm but ≤4 cm in greatest dimension, limited to the thyroid
T3 tumour >4 cm in greatest dimension limited to the thyroid or any tumour with minimal
extrathyroidal extension (e.g. extension to sternothyroid muscle or peri-thyroid soft
tissues)
T4 tumour of any size extending beyond the thyroid capsule
T4a tumour invades subcutaneous soft tissues, larynx, trachea, oesophagus or recurrent
laryngeal nerve
T4b tumour invades pre-vertebral fascia or encases carotid artery or mediastinal vessel
NX regional lymph nodes cannot be assessed
N0 no regional lymph node metastasis
N1 regional lymph node metastasis
N1a metastases to level VI (pretracheal, paratracheal and prelaryngeal/Delphian lymph
nodes)
N1b metastases to unilateral, bilateral, or contralateral cervical (levels I–IV or V) or
retropharyngeal or superior mediastinal lymph nodes (level VII)
MX distant metastases cannot be assessed
M0 no distant metastasis
M1 distant metastasis
RX cannot assess presence of residual primary tumour
R0 no residual primary tumour
R1 microscopic residual primary tumour
R2 macroscopic residual primary tumour

nodes. Therapeutic level VI nodal dissection is recom- recurrent laryngeal nerves should be attempted in
mended when the presence of lymph node metastasis is almost all cases. Extensive resection of trachea,
confirmed. larynx and oesophagus should be considered if poten-
Clinically involved lateral cervical lymph nodes tially curative. Where disease is unresectable, radio-
should be managed by selective neck dissection therapy and radioiodine should be considered.
(levels II–V). Involvement of level I or VII node is
rare in DTC and should only be dissected if involved. Microcarcinomas. Microcarcinomas are differentiated
Prophylactic lateral neck compartment dissection for thyroid carcinomas less than 10 mm in maximum
node negative patients is not recommended. dimension and are predominantly papillary carcin-
omas. The management of papillary microcarcinomas
Completion thyroidectomy. Completion thyroidectomy is outlined in Figure 1.
is not needed in low-risk, unifocal, intrathyroidal
tumours less than 4 cm in diameter, with clinically
Recommendations
negative lymph nodes.
• In patients with thyroid cancer, assessment of
Locally advanced disease. Where possible, locally
extrathyroidal extension and lymph node
advanced disease should be resected. Preservation of
disease in the central and lateral neck
compartments should be undertaken pre-
TABLE IV operatively by USS and cross-sectional
GROUP STAGING AND SURVIVAL FOR imaging (CT or MRI) if indicated (R)
DIFFERENTIATED THYROID CANCER
• For patients with Thy 3f or Thy 4 FNAC a
Stage Age <45 Age >45 years 10-year diagnostic hemithyroidectomy is
years survival (%) recommended (R)
I Any T, any T1, N0, M0 98.5 • Total thyroidectomy is recommended for
N, M0 patients with tumours greater than 4 cm in
II Any T, any T2, N0, M0 98.8
N, M1 diameter, or tumours of any size in
III T3, N0, M0 or T1–3, 99.0 association with any of the following
N1a, M0 characteristics: multifocal disease, bilateral
∗
IVA T4a, any N, M0 or 75.9
T1–3, N1b, M0 disease, extrathyroidal spread (pT3 and
IVB T4b, any N, M0 62.5 pT4a), familial disease, and those with
IVC Any T, any N, M1 63.0 clinically or radiologically involved nodes
∗ and/or distant metastases (R)
Undifferentiated or anaplastic carcinomas are all stage IV
MANAGEMENT OF THYROID CANCER: UK GUIDELINES S155

• Subtotal thyroidectomy should not be used in
the management of thyroid cancer (G)
• Central compartment neck dissection is not
recommended for patients without clinical or
radiological evidence of lymph node
involvement, provided they meet all of the
following criteria: classical type PTC, below
45 years, unifocal tumour, less than 4 cm, no
extrathyroidal extension on US (R)
• Patients with metastases in the lateral
compartment should undergo therapeutic
lateral and central compartment neck
dissection (R)
• Patients with follicular tumours greater
than 4 cm should be treated with total
thyroidectomy (R)
All patients with thyroid cancer should be clinically
staged using the TNM classification and also scored
using one of the clinicopathological scoring systems
to enable planned follow-up, identification of high
risk patients and those who would benefit from
radio-iodine therapy. In addition, all patients should
have access to a thyroid cancer clinical nurse specialist
and be given written information.
Persistent voice dysfunction should be investigated
and referral to a specialised practitioner for assessment
and speech therapy sought.
Patients with long-term hypocalcaemia (hypopara-
thyroidism) should have their calcium levels regularly
monitored either in association with an endocrinologist
or with their GP.
Following surgery, initial post-operative risk stratifi-
cation for risk of recurrence can occur.
Low-risk patients have the following
characteristics:

Post-operative management • No local or distant metastases

After total or near total thyroidectomy patients should
be commenced on suppressive doses of levothyroxine
(2 μg/kg) or liothyronine 20 mcg tds in accordance
with local protocols.
Calcium levels should be routinely checked within
24 hours and hypocalcaemia treated appropriately.
Thyroglobulin levels should be checked no earlier
than six weeks after surgery.
• All macroscopic tumours have been resected, i.e.
R0 or R1 resection
• No tumour invasion of locoregional tissues or
structures
• The tumour does not have aggressive histology
(tall cell or columnar cell PTC, diffuse sclerosing
PTC, poorly differentiated elements) or
angioinvasion.

TABLE V
INITIAL SURGERY FOR PAPILLARY THYROID CARCINOMA
Tumour <4 cm Tumours >/=4 cm T3 and T4 tumours
+N1 level VI nodes,
M1
Recommendation With no other clinical features Papillary cancer diagnosed Treat all above tumours
such as age >45 years, following hemithyroidectomy, as high risk
extrathyroidal spread, nodal multifocal disease, thyroid
involvement, angioinvasion, radiation in childhood, familial
multifocality, distant disease (first degree relative)
metastases
Hemithyroidectomy Yes No No
Total thyroidectomy Discuss at MDT Completion total thyroidectomy Yes
Prophylactic level VI nodal dissection No Personalised decision making Yes
Therapeutic level VI nodal dissection Yes Yes Yes
(clinically involved)

TABLE VI
INITIAL SURGERY FOR FOLLICULAR THYROID CANCER
Clinical details
Recommendation Low-risk patient (with all of following) High-risk patient (one or more of the following)
<45 years >45 years
>1–≤4 cm Tumour >4 cm
Minimally invasive Extra-capsular invasion
No angioinvasion Extrathyroidal disease
No extracapsular invasion Widely invasive
No extrathyroidal spread Angioinvasion
Hurthle cell tumours
Hemithyroidectomy Yes No
Total thyroidectomy No Yes
Level VI nodal dissection No Only where clinically involved nodes present
S156 A L MITCHELL, A GANDHI, D SCOTT-COOMBES et al.

FIG. 1
Flow diagram outlining management of papillary microcarcinomas. Multiple risk factors may tip the balance in favour of total thyroidectomy.

Intermediate-risk patients have any of the following

characteristics:
TABLE VII
• Microscopic invasion of tumour into the peri-thyr- INDICATIONS FOR I131 ABLATION FOLLOWING TOTAL
oidal soft tissues (T3) at initial surgery THYROIDECTOMY FOR DIFFERENTIATED THYROID
CANCER
• Cervical lymph node metastases (N1a or N1b)
• Tumour with aggressive histology (tall cell or col- Recommendation Clinical details
umnar cell PTC, diffuse sclerosing PTC, poorly Definite I131 ablation Tumour >4 cm
differentiated elements) or angioinvasion. Any tumour size with gross
extrathyroidal extension
Distant metastases present
High-risk patients have any of the following Risk factors indicating higher
characteristics: risk of recurrence where I131
should be considered include:
Large tumour size
• Extrathyroidal invasion Probable I131 ablation Extrathyroidal extension
• Incomplete macroscopic tumour resection (R2) Consider on individual Unfavourable cell type (tall cell,
• Distant metastases. (M1) case merit (MDT) columnar or diffuse sclerosing
papillary cancer, poorly
differentiated elements)
Widely invasive histology
Radioiodine (I131) ablation and external beam Multiple lymph node
radiotherapy (EBR) in DTC involvement, large size of
involved lymph nodes, high
The current recommendations with regards to I131 abla- ratio of positive-to-negative
tion following total thyroidectomy are outlined in nodes, extracapsular nodal
Table VII. involvement
No I131 ablation (all Tumour <1 cm unifocal or
Patients should be prepared for I131 by having a low- criteria must be met) multifocal
iodine diet for one to two weeks prior to treatment. Histology classical papillary or
Recombinant TSH (rhTSH) therapy prior to I131 is follicular variant of papillary
carcinoma, or follicular
preferable to thyroid hormone withdrawal, and is pre- carcinoma
ferred by patients, providing they meet the following Minimally invasive without
criteria: pT1 to T3, pN0 or NX or N1, and M0 and angioinvasion
No invasion of thyroid capsule
R0 (no microscopic residual disease). Pregnancy (extrathyroidal extension)
should be excluded prior to giving I131. A post-ablation
MANAGEMENT OF THYROID CANCER: UK GUIDELINES S157

scan should be performed after I131 when residual suspicious of recurrent disease. Thyroglobulin evalu-
activity levels permit satisfactory imaging. Practically, ation is most effective following TSH stimulation,
this is generally 2–10 days following treatment. either by direct rhTSH stimulation or by withdrawal
Following I131, TSH should be suppressed to of thyroid hormone replacement.
<0.1 mIU/l pending dynamic risk stratification at Following total or near total thyroidectomy and I131
9–12 months. ablation, low-risk patients with undetectable Tg levels
Adjuvant EBR should be considered in unresectable on TSH suppression should have a TSH-stimulated
tumours in addition to I131 and where there is residual Tg assessment along with ultrasound of cervical
disease following surgical resection even if the residual nodes at 9–12 months following I131 ablation. If Tg
tumour concentrates I131. levels remain undetectable following TSH stimulation,
In the 9 to 12 months following surgery and I131 for then future recurrent disease is highly unlikely and
DTC with an R0 resection, patients should undergo patients may revert to yearly Tg estimation whilst
dynamic risk stratification (Table VIII). Patients are remaining on TSH suppression.
then categorised as having either an excellent response, A rise in Tg may be suggestive of recurrent or residual
an indeterminate response or an incomplete response. disease, but is usually from a thyroid remnant. In low-
risk patients, an expectant policy can be maintained
Monitoring Tg levels. Thyroglobulin monitoring is most and repeated TSH stimulated assessment performed,
effective following total or near total thyroidectomy with the expectation that Tg levels will fall. Rising or
and I131 and is an important modality in detecting persistently elevated Tg needs further evaluation.
residual or recurrent disease. Physicians should be The use of rhTSH-stimulated Tg estimation or
aware that Tg estimations vary according to the assay rhTSH I131 therapy is necessary in the following
method, the individual laboratory and the presence of cases: hypopituitarism, functional metastases (suppres-
anti-Tg antibodies and take these considerations into sing TSH), severe angina, advanced disease (frail
account when evaluating Tg levels in individual patient) and history of psychiatric disturbance from
patients. hypothyroidism.
The patient should have their Tg levels checked at
6–12 monthly intervals. Rising Tg levels are highly
Recommendations
TABLE VIII • I131 ablation or therapy should be carried out
DYNAMIC RISK STRATIFICATION FOLLOWING only in centres with appropriate facilities (R)
TREATMENT FOR DTC AND TSH SUPPRESSION
TARGETS FOR PATIENTS TREATED WITH TOTAL • Serum Tg should be checked in all post-
THYROIDECTOMY AND I131 ABLATION WITH operative patients with DTC, but not earlier
R0 RESECTION than six weeks after surgery (R)
Excellent response Indeterminate Incomplete response • Patients who have undergone total or near
response
total thyroidectomy should be started on
All the following: Any of the Any of the following: levothyroxine 2 μg/kg or liothyronine 20 mcg
Suppressed and following: Suppressed tds after surgery (R)
stimulated Suppressed Tg ≥ 1 lg/l∗ or
Tg < 1 lg/l∗ Tg < 1 lg/l∗ stimulated • The majority of patients with a tumour more
Neck US without and stimulated Tg ≥ 10 lg/l∗ than 1 cm in diameter, who have undergone
evidence of Tg ≥ 1 and Rising Tg values
disease <10 lg/l∗ Persistent or newly total or near-total thyroidectomy, should have
Cross-sectional Neck US with identified disease I131 ablation or therapy (R)
and/or nuclear non-specific on cross-sectional
medicine changes or and/or nuclear • A post-ablation scan should be performed
imaging stable sub medicine imaging 3–10 days after I131 ablation (R)
negative (if centimetre
performed) lymph nodes • Post-therapy dynamic risk stratification at
Cross-sectional 9–12 months is used to guide further
and/or nuclear management (G)
medicine
imaging with
non-specific
changes, Persistent and recurrent disease, locoregional
although not
completely
recurrence and distant metastases
normal Potentially resectable disease is best managed by
Low risk Intermediate risk High risk
Maintain TSH Suppress TSH Suppress
surgery (including local cervical nodes and soft tissue
0.3–2.0 mIU/l 0.1–0.5 mIU/l TSH < 0.1 mIU/l disease in the neck), followed by I131. Residual
for 5–10 years indefinitely disease not amenable to resection or resistant to I131
then reassess
therapy is best treated with high dose palliative EBR.
∗
Assumes the absence of interference in the Tg assay. Tg = thyro- Therapeutic central compartment, with or without
globulin; TSH = thyroid stimulating hormone; US = ultrasound lateral compartment, nodal clearance should therefore
S158
be performed for all persistent or recurrent disease con-
fined to the neck. Impalpable nodes greater than
5–8 mm seen on USS or cross-sectional imaging follow-
ing I131 therapy should be considered for removal.
Removing nodes less than 5–8 mm has not be shown
to be of benefit.
Where technically feasible, tumours invading the
aero-digestive tract should be resected in combination
with radiotherapy. Outcome is very dependent on com-
pleteness of resection and preservation of function.
Great care should therefore be taken in the selection
and discussion of such patients at the MDT.
Distant metastases develop in 5–23 per cent of patients
with DTC. Sites not amenable to surgical resection should
be treated with I131 therapy. Long-term survival may be
expected in patients whose tumours take up I131. Distant
metastases are usually seen in the lungs and bones.
There is no maximum limit to the cumulative dose of
I131 that patients with persistent disease may receive and
pulmonary fibrosis appears to be a rare side effect.
Surgical resection of bony metastases should be consid-
ered (especially in patients below 45 years of age).
Metastases not cured by I131 should be treated with
EBR. Other modalities such as intra-arterial embolisation,
pamidronate infusion, radiofrequency ablation or verteb-
roplasty may be considered in cases of painful lesions.
Recommendations
• Potentially resectable recurrent or persistent
disease should be managed with surgery
whenever possible (R)
• Distant metastases and sites not amenable to
surgery, which are iodine avid should be
treated with I131 therapy (R)
Long-term follow-up
Lifelong follow-up of DTC is recommended to monitor
for late recurrence (often treatable and curable), effects
of long-term TSH suppression (atrial fibrillation and
osteoporosis) and late side effects of I131. Clinical
examination and history, Tg determination, TSH sup-
pression and where necessary calcium monitoring
should all be performed. Ultrasound scanning as per
established protocols may also be undertaken.
Recommendations
• Long-term follow-up for patients with DTC is
recommended (G)
• Follow-up should be based on clinical
examination, serum Tg and TSH
assessments (R)
A L MITCHELL, A GANDHI, D SCOTT-COOMBES et al.
Medullary thyroid cancer
Introduction
Medullary thyroid cancer (MTC) is a rare cancer
(approximately 1–3 per cent of all thyroid cancer
cases). All cases should be referred for surgical treat-
ment to the designated cancer centre of the Thyroid
Cancer Network. Twenty-five per cent of MTC cases
are familial (MEN2A, MEN2B and familial non-
MEN MTC). Genetic screening (RET mutation
testing) of all patients is mandatory and the assessment,
investigation and treatment of family members at
potential risk requires a multidisciplinary approach
within the cancer centre.7
Clinical presentation
Patients usually present clinically with a thyroid nodule
or neck mass with or without cervical lymphadenop-
athy (in the same fashion as with DTC). History
however, may reveal other symptoms such as flushing,
loose stools or diarrhoea (which suggest MTC) and is
vitally important in determining a potential familial
element. FNAC may be diagnostic (when combined
with calcitonin staining in suspicious cases), but
often is reported as Thy 3.
Investigation
When MTC is suspected (or proven) patients must
undergo the following investigations prior to surgery8:
• Calcitonin and CEA levels
• Twenty-four-hours urine estimation of cate-
cholamines and nor metanephrines (or plasma
nor metanephrines) to identify or exclude phaeo-
chromocytoma
• Serum calcium and parathyroid hormone (PTH) to
identify or exclude hyperparathyroidism
• CT, MRI or USS of the neck are indicated as they
may help guide the extent of surgical resection at
initial surgery
• RET proto-oncogene mutational analysis should
be performed after surgery once diagnosis is
established, even in the absence of a familial
history.
Staging
TNM staging for MTC follows the same criteria as for
DTC (Table IX).
TABLE IX
GROUP STAGING FOR MEDULLARY THYROID CANCER
Stage I T1, N0, M0
Stage II T2, T3, T4, N0, M0
Stage III Any T, N1, M0
Stage IV Any T, any N, M1
MANAGEMENT OF THYROID CANCER: UK GUIDELINES
Recommendations
• Patients with suspected MTC should be
investigated with calcitonin and CEA levels,
24 hours catecholamine and nor
metanephrine urine estimation (or plasma
free nor metanephrine estimation), serum
calcium and PTH (R)
• Relevant imaging studies are advisable to
guide the extent of surgery (R)
• RET proto-oncogene analysis should be
performed after surgery (R)
Management-surgery for MTC
All patients with MTC should undergo8:
• Total thyroidectomy and central compartment
node clearance (level VI). This should be per-
formed even in the presence of disseminated
metastases to control local disease.
• In the presence of central compartment lymph
node metastases, ipsilateral prophylactic neck dis-
section is recommended as up to 70 per cent of
patients will have lateral nodal metastases.
• Patients with clinically involved lateral compart-
ment nodes should have a therapeutic lateral
neck dissection to eradicate local disease.
• All T2–T4 tumours should also undergo prophy-
lactic bilateral selective neck dissection IIa–Vb.
• Intra-thoracic disease below the level of the bra-
chiocephalic vein should be resected via sternot-
omy where feasible.
• Prophylactic thyroidectomy should be offered to
RET-positive family members. Timing and
extent of surgery are dependent on genotype
(codon mutation), the calcitonin level and age at
detection of RET positivity.
Persistent or recurrent MTC
Calcitonin levels are most informative six months after
initial surgery. It is important to distinguish persistent
locoregional disease (following either inadequate
initial surgery or local lymph node metastases) from
distant disease.
Early local recurrence following adequate local
surgery (total thyroidectomy and level VI nodes) is
unusual. The likely source of raised calcitonin in this
circumstance is the lateral compartment cervical
nodes, i.e. persistent disease. When indicated, re-
operation including further central compartment
surgery and lateral neck node dissection should be per-
formed. The primary aim should always be to control
local disease.
CT, MRI, USS, selective arteriography, I131-metaio-
dobenzylguanidine, 18Fluoro-deoxy-glucose positron
S159
emission tomography, In111-octreotide and direct laparo-
scopic visualisation of the liver may all be useful in
identifying the source of a raised calcitonin, but their
use in patients with calcitonin levels <400–500 pg/
ml is unlikely to identify metastases. When indicated,
isolated metastases should be considered for surgical
resection.
Recommendations
• All patients with known or suspected MTC
should have serum calcitonin and biochemical
screening for phaeochromocytoma pre-
operatively (R)
• All patients with proven MTC >5 mm should
undergo total thyroidectomy and central
compartment neck dissection (R)
• Patients with lateral nodal involvement should
undergo selective neck dissection (IIa–Vb)
(R)
• Patients with central node metastases should
undergo ipsilateral prophylactic lateral node
dissection (R)
• Prophylactic thyroidectomy should be offered
to RET-positive family members (R)
• All patients with proven MTC should have
genetic screening (R)
Radiotherapy and chemotherapy
Radiotherapy is of use in controlling local symptoms in
patients with inoperable disease and improving the
relapse-free rate following central or lateral compart-
ment surgery where residual disease is present macro-
scopically or microscopically.
Tyrosine kinase inhibitors can be effective in con-
trolling symptoms in patients with metastatic disease.
Somatostatin analogues may be effective in alleviat-
ing the unpleasant gastrointestinal symptoms that
patients with advanced cases of MTC experience.
Recommendations
• Radiotherapy may be useful in controlling
local symptoms in patients with inoperable
disease (R)
• Chemotherapy with tyrosine kinase inhibitors
may help in controlling local symptoms (R)
Follow-up
Lifelong follow-up is recommended for all patients
with MTC. Screening should include calcitonin and
CEA. Thyroid-stimulating hormone suppression is
not necessary. Rising calcitonin levels should trigger
S160
investigations to identify potentially treatable metastat-
ic disease.
Anaplastic thyroid cancer
The prognosis of patients with anaplastic thyroid
cancer (ATC) is poor. Many patients present with a
history of a rapidly enlarging thyroid mass in a long-
standing goitre. Diagnosis can be established by fine
needle aspiration or core biopsy. Core biopsy will
help differentiate ATC from thyroid lymphoma which
can present in a similar manner.
Total thyroidectomy may be curative for very small
cancers. In more advanced disease surgery may be of
benefit if R0/R1 resection is achievable.9 External
beam radiotherapy and chemotherapy may be used as
adjuvant treatments in patients with R0/R1 resection
and no evidence of distant disease. ‘Debulking’
surgery should be avoided when complete resection
cannot be achieved. Palliative chemoradiation may be
of some value in selected cases. Palliative care has a
principal role in management of these patients.
Recommendations
• Initial assessment should focus on identifying
the small proportion of patients with localised
disease and good performance status, who
may benefit from surgical resection and other
adjuvant therapies (G)
• The surgical intent should be gross tumour
resection and not merely an attempt at
debulking (G)
A L MITCHELL, A GANDHI, D SCOTT-COOMBES et al.
References
1 Perros P, Boelaert K, Colley S, Evans C, Evans RM, Gerrard
Ba G et al. Guidelines for the management of thyroid cancer.
Clin Endocrinol (Oxf ) 2014;81(Suppl 1):1–122
2 Haugen BRM, Alexander EK, Bible KC, Doherty G, Mandel SJ,
Nikiforov YE et al. American thyroid association management
guidelines for adult patients with thyroid nodules and differen-
tiated thyroid cancer. Thyroid 2016;26:1–133
3 Francis GL, Waguespack SG, Bauer AJ, Angelos P, Benvenga S,
Cerutti JM et al. Management guidelines for children with thyroid
nodules and differentiated thyroid cancer. Thyroid 2015;25:716–59
4 Lorenz K, Niederle B, Steinmuller T, Dralle H. The European
Society of Endocrine Surgeons perspective of thyroid cancer
surgery: an evidence-based approach. Langenbecks Arch Surg
2014;399:135–9
5 Leenhardt L, Erdogan MF, Hegedus L, Mandel SJ, Paschke R,
Rago T et al. 2013 European thyroid association guidelines for
cervical ultrasound scan and ultrasound-guided techniques in
the postoperative management of patients with thyroid cancer.
Eur Thyroid J 2013;2:147–59
6 Sancho JJ, Lennard TW, Paunovic I, Triponez F, Sitges-Serra A.
Prophylactic central neck disection in papillary thyroid cancer: a
consensus report of the European Society of Endocrine Surgeons
(ESES). Langenbecks Arch Surg 2014;399:155–63
7 Niederle B, Sebag F, Brauckhoff M. Timing and extent of thyroid
surgery for gene carriers of hereditary C cell disease – a consen-
sus statement of the European Society of Endocrine Surgeons
(ESES). Langenbecks Arch Surg 2014;399:185–97
8 Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF
et al. Revised American Thyroid Association guidelines for the
management of medullary thyroid carcinoma. Thyroid 2015;25:
567–610
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KD et al. American Thyroid Association guidelines for manage-
ment of patients with anaplastic thyroid cancer. Thyroid 2012;22:
1104–39
Address for correspondence:
Anna L. Mitchell,
The Newcastle upon Tyne Hospitals NHS Foundation Trust,
Newcastle upon Tyne, UK
E-mail: annamitchell@doctors.org.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S161–S169. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S002221511600058X

Management of neck metastases in head and neck

cancer: United Kingdom National Multidisciplinary
Guidelines

V PALERI1, T G URBANO2, H MEHANNA3, C REPANOS4, J LANCASTER5, T ROQUES6,

M PATEL7, M SEN8
1
Department of Otolaryngology – Head and Neck Surgery, The Newcastle upon Tyne Hospitals NHS Foundation
Trust, Northern Institute of Cancer Research, Newcastle upon Tyne, 2Department of Oncology, Guy’s and St
Thomas’ Hospitals, London, 3Institute of Head and Neck Studies and Education, University of Birmingham,
University Hospital, Birmingham, 4Department of Otolaryngology – Head and Neck Surgery, Queen Alexandra
Hospital, Portsmouth, 5Department of Otolaryngology – Head and Neck Surgery, University Hospital Aintree,
Liverpool, 6Department of Clinical Oncology, Norfolk and Norwich University Hospital, Norwich, 7Department of
Oral and Maxillofacial Surgery, University Hospital of South Manchester NHS Foundation Trust, Manchester, and
8
Department of Clinical Oncology, St James’s Institute of Oncology, Leeds, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. A rational plan to manage the neck is necessary for all head and neck primaries. With the
emergence of new level 1 evidence across several domains of neck metastases, this guideline will identify the
evidence-based recommendations for management.

Recommendations
• Computed tomographic or magnetic resonance imaging is mandatory for staging neck disease, with choice of
modality dependant on imaging modality used for the primary site, local availability and expertise. (R)
• Patients with a clinically N0 neck, with more than 15–20 per cent risk of occult nodal metastases, should be
offered prophylactic treatment of the neck. (R)
• The treatment choice of for the N0 and N+ neck should be guided by the treatment to the primary site. (G)
• If observation is planned for the N0 neck, this should be supplemented by regular ultrasonograms to ensure
early detection. (R)
• All patients with T1 and T2 oral cavity cancer and N0 neck should receive prophylactic neck treatment. (R)
• Selective neck dissection (SND) is as effective as modified radical neck dissection for controlling regional
disease in N0 necks for all primary sites. (R)
• SND alone is adequate treatment for pN1 neck disease without adverse histological features. (R)
• Post-operative radiation for adverse histologic features following SND confers control rates comparable with
more extensive procedures. (R)
• Adjuvant radiation following surgery for patients with adverse histological features improves regional control rates. (R)
• Post-operative chemoradiation improves regional control in patients with extracapsular spread and/or microscopically
involved surgical margins. (R)
• Following chemoradiation therapy, complete responders who do not show evidence of active disease on co-registered
positron emission tomography–computed tomography (PET–CT) scans performed at 10–12 weeks, do not need
salvage neck dissection. (R)
• Salvage surgery should be considered for those with incomplete or equivocal response of nodal disease on PET–CT. (R)

Introduction of disease. Controversy surrounds the management

The presence, site and size of metastatic neck disease
are important prognostic factors in head and neck
squamous cell cancer. Head and neck tumours have
a propensity to metastasise to neck nodes and
several factors control the natural history and spread
of the neck in head and neck squamous cell cancer.
This is primarily due to the paucity of high-level evi-
dence for many treatment paradigms, but this trend
may be reversing with randomised controlled trials
and systematic reviews published recently and a few
S162
more in progress. This section discusses the manage-
ment of neck metastases at initial presentation and for
residual or recurrent neck disease. It outlines major
clinical controversies regarding the management of
occult and overt metastatic squamous cell carcinoma
(SCC) to the neck nodes.
Assessment and staging
For the purpose of assessment and documentation, the
neck is described in six anatomical levels, (Table I).
Level VII is relevant for some head and neck
tumours and is included in the table for completeness.
Clinical palpation
Clinical palpation is regarded as inaccurate (sensitivity
and specificity 70–80 per cent) due to factors including
inter-operator variability, shape of neck, absence or
presence of significant subcutaneous fat and varying
size of involved cervical nodes.
Computed tomographic (CT) and magnetic resonance
imaging (MRI) scanning
These techniques have similar sensitivity (81 per cent)
in detecting metastatic disease, with CT demonstrating
better specificity.1 Co-registered positron emission
tomography–computed tomography scanning (PET–
CT) has been shown to alter initial staging in up to
one-third of patients, but the value of this is unclear.
This technique has higher sensitivity in picking up clin-
ically occult primaries, synchronous second primaries
and distant metastases. PET-CT has demonstrated
high negative predictive values in the assessment of
neck disease after organ preservation regimes.
Ultrasound (US) scanning and US-guided fine needle
aspiration cytology (FNAC)
Ultrasound has been demonstrated to have consistent-
ly high sensitivity (87 per cent) in diagnosing meta-
static neck disease. Ultrasound-guided FNAC
requires both expertise and experience, and has very
high specificity rates (98 per cent) in diagnosis. It
should be noted that there are no absolute ultrasound
characteristics for differentiating benign from malig-
nant disease.
Sentinel node biopsy
The aim of this technique is to identify and excise the
echelon nodes using radioscintigraphy, which are
then tested for occult disease. Patients with no occult
disease in the sentinel nodes receive no further treat-
ment for the neck. Meta-analyses suggest that sentinel
node biopsy has sensitivity rates exceeding 90 per
cent.2,3 A recent prospective multicentre study that
recruited 415 patients with 0.5–4 cm transorally resect-
able SCC and an N0 neck, showed that sentinel node
biopsy had a sensitivity, negative predictive value and
false negative rate of 86, 95 and 14 per cent, respective-
ly.4 Oncological outcomes were not compromised
V PALERI, T G URBANO, H MEHANNA et al.
despite only 94 of 415 patients undergoing neck dissec-
tion in this cohort.
Recommendation
• Computed tomographic or MR imaging is
mandatory for staging neck disease, with
choice of modality dependent on imaging
modality used for the primary site, local
availability and expertise (R)
Neck nodal stage
This should be confirmed and documented in the
case record after imaging (certainty factor 2) and
prior to treatment planning, using the N category in
the 7th edition of the TNM Classification of
Malignant Tumours, Union for International Cancer
Control (UICC) cancer staging manual. Table II
shows the N category to stage neck metastases
arising from all head and neck sites excluding
those of the nasopharynx, thyroid gland and
mucosal melanomas.
Treatment options
Surgery
Historically the mainstay of surgical management of
metastatic neck has been neck dissection in its
various forms. The standardised neck dissection ter-
minology produced by the American Academy of
Otolaryngology and Head and Neck Surgery in 1991
has been updated by the Committee for Neck
Dissection Classification of the American Head and
Neck Society in 20025 (Table III). There is an increas-
ing trend to divide neck dissections into two broad
types with subdivisions: comprehensive (removal of
levels I–V) and selective (less than five levels). The
need for less extensive surgery in the chemoradiation
era, with neck dissection procedures that cannot be
classified under the existing systems has led to calls
for revision of this system.6
It is recommended that the levels or sublevels
removed during selective neck dissection (SND) be
precisely stated in the operation notes. In order to min-
imise confusion within labelling the levels during pro-
cessing, the neck dissection specimen should be
divided according to the levels in the operating room
and sent to the laboratory in different containers. An
alternative is to orientate the neck dissection specimen
on a suitable base and label the levels with a marking
pen, with or without a photograph, and send it to the
laboratory. There is good evidence for reduced long-
term morbidity with SND compared with the compre-
hensive types, namely modified radical neck dissection
(MRND) and radical neck dissection (RND). Surgical
NECK METASTASES IN HEAD AND NECK CANCER: UK GUIDELINES S163

TABLE I
LYMPH NODE LEVELS, SUBLEVELS AND BOUNDARIES
Level Clinical location Surgical boundaries Radiological boundaries

Ia Submental triangle S: Symphysis of mandible Nodes above the level of lower body of hyoid bone,
I: Hyoid bone below mylohyoid muscles and anterior to a
A (M): Left anterior belly of digastric transverse line drawn through the posterior edge of
P (L): Right anterior belly of digastric submandibular gland on an axial image
Ib Submandibular S: Body of mandible
triangle I: Posterior belly of digastric
A (M): Anterior belly of digastric
P (L): Stylohyoid muscle
IIa Upper jugular S: Lower level of bony margin of jugular fossa Superior and inferior limits as described under
I: Level of lower body of hyoid bone surgical boundaries
A (M): Stylohyoid muscle Nodes posterior to a transverse plane defined by the
P (L): Vertical plane defined by accessory nerve posterior surface of submandibular gland and
IIb Upper jugular S: Lower level of bony margin of jugular fossa anterior to a transverse line drawn along the
I: Level of lower body of hyoid bone posterior border of the sternomastoid.
A (M): Vertical plane defined by accessory NOTE: Nodes lying medial to the carotids are
nerve retropharyngeal and not level II
P (L): Posterior border of sternomastoid muscle
III Mid Jugular S: Level of lower body of hyoid bone Superior and inferior limits as described under
I: Horizontal plane along inferior border of surgical boundaries
anterior cricoid arch Nodes anterior to a transverse line drawn on each
A (M): Lateral border of sternohyoid muscle axial scan through the posterior edge of the SCM
P (L): Posterior border of sternocleidomastoid and lateral to the medial margin of the common
muscle or sensory branches of the cervical carotid arteries
plexus
IV Lower jugular S: Horizontal plane along inferior border of Superior and inferior limits as described under
anterior cricoid arch surgical boundaries
I: Clavicle Nodes anterior to a transverse line drawn on each
A (M): Lateral border of sternohyoid muscle axial scan through the posterior edge of the SCM
P (L): Posterior border of sternocleidomastoid and lateral to the medial margin of the common
muscle or sensory branches of the cervical carotid arteries
plexus
Va Posterior triangle S: Convergence of SCM and trapezius muscles Nodes posterior to a transverse line drawn on each
I: Horizontal plane along inferior border of axial scan through the posterior edge of the SCM
anterior cricoid arch
A (M): Posterior border of sternocleidomastoid
muscle or sensory branches of the cervical
plexus
P (L): Anterior border of trapezius muscle
Vb Posterior triangle S: Horizontal plane along inferior border of
(supraclavicular) anterior cricoid arch
I: Clavicle
A (M): Posterior border of sternocleidomastoid
muscle or sensory branches of the cervical
plexus.
P (L): Anterior border of trapezius muscle
VI Anterior S: Hyoid bone
compartment I: Sternal notch
A (M): Common carotid artery
P (L): Common carotid artery
VII Superior S: Sternal notch
mediastinum I: Innominate artery
A (M): Common carotid artery
P (L): Common carotid artery
S = superior; I = inferior, A = anterior; P = posterior, L = lateral; M = medial; SCM = sternocleidomastoid

therapy must be delivered within accredited multidis-
ciplinary teams, by members regularly involved in
caring for head and neck cancer patients.
Radiotherapy
Radiotherapy (RT) should be delivered within an
accredited department using megavoltage photons
typically from a linear accelerator (typical energy
6 MV). Similar principles should be used for selecting
the nodes for RT as are described above for surgery.
The probability of microscopic involvement of other
nodal groups rises with increasing T-stage and this
leads to larger volumes of tissue-requiring irradiation.
Radiotherapy to the neck requires adequate immobil-
isation and a five-point fixation shell is recommended.
Computed tomography scanning in the treatment pos-
ition provides the anatomical and electron density infor-
mation required for RT planning. Conventional and
three-dimensional conformal RT often require the use
of multiple phases of treatment using photons and elec-
trons of appropriate energy. These techniques have now
been superseded by intensity modulated radiotherapy
(IMRT), particularly where bilateral nodal irradiation
S164 V PALERI, T G URBANO, H MEHANNA et al.

TABLE II after RNDs in patients with clinically node negative

TUMOUR–NODE–METASTASIS CLASSIFICATION OF
REGIONAL NODES
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastases
N1 Metastasis in a single ipsilateral lymph node 3 cm or less in
greatest dimension
N2 Metastasis in a single ipsilateral lymph node, more than
3 cm but not more than 6 cm in greatest dimension, or in
multiple ipsilateral lymph nodes none more than 6 cm in
greatest dimension, or in bilateral or contralateral lymph
nodes, none more than 6 cm in greatest dimension
N2a Metastasis in a single ipsilateral lymph node, more than
3 cm but not more than 6 cm in greatest dimension
N2b Metastasis in multiple ipsilateral lymph nodes, none more
than 6 cm in greatest dimension
N2c Metastasis in bilateral or contralateral lymph nodes, none
more than 6 cm in greatest dimension
N3 Metastasis in a lymph node more than 6 cm in greatest
dimension
Note: Midline nodes are considered to be ipsilateral nodes
is indicated, where it has been shown to be associated
with a reduced risk of late xerostomia and has become
the standard of care.
There is now increasing use of concomitant chemo-
radiotherapy following publication of level 1 studies,
suggesting that use of chemoradiotherapy improves
overall and progression free survival in advanced head
and neck cancer both in the primary and post-operative set-
tings. Altered fractionation regimes have also been shown
to offer some advantage over standard fractionation.
Management strategies for the various neck
nodal stages
(N0) necks. These figures are useful in identifying the
risk of occult metastases in N0 necks and are used to
guide clinicians when deciding whether prophylactic
treatment of the neck is appropriate (Figure 1).
A study of risk–benefit analysis made in the 1990s
using data from retrospective series, when RND was
the only procedure widely used for elective neck treat-
ment, suggested that prophylactic treatment of the neck
was required if the risk of occult nodal metastases rose
above 20 per cent. Given the low morbidity of either
available treatment modality, there is support for elect-
ive treatment for lesser risk (5–15 per cent). Primary
sites with greater than 15 per cent risk of occult meta-
static disease in the neck would include almost all squa-
mous cancers of the upper aerodigestive tract except T1
and T2 cancers of the glottis and selected T1 cancers of
the oral cavity.
A recent randomised controlled trial (RCT) reported
on 500 patients with lateralised stage T1 or T2 oral
SCCs randomised to elective neck dissection (n =
245) or observation and intervention (n = 255), with
a median follow up period of 39 months.7 At three
years, elective node dissection resulted in an
improved rate of overall survival (80.0 per cent;
95 per cent confidence interval (CI), 74.1 to 85.8), as
compared with therapeutic dissection (67.5 per cent;
95 per cent CI, 61.0 to 73.9), with a hazard ratio for
death of 0.64 in the elective-surgery group (95 per
cent CI, 0.45 to 0.92; p = 0.01 by the log-rank test).
Patients in the elective-surgery group also had a
higher rate of disease-free survival than those in the
therapeutic-surgery group (69.5 per cent vs 45.9 per

Treatment of cervical lymph nodes is either elective (in

the clinically negative neck) or therapeutic (in the clin-
ically positive neck).

Management of the clinically node negative neck (N0)

New primary. Clinical and radiological examinations are
unable to detect microscopic disease in lymph nodes.
Several large retrospective series have reported the inci-
dence of metastases found on histological examination

TABLE III
CLASSIFICATION OF NECK DISSECTION TECHNIQUES
Radical neck Removal of levels I–V, accessory nerve,
dissection (RND) internal jugular vein and sternomastoid
muscle
Modified radical Removal of levels I–V dissected;
neck dissection preservation of one or more of the
accessory nerve, internal jugular vein
or sternomastoid muscle (types I, II,
III, respectively)
Selective neck Preservation of one or more levels of
dissection lymph nodes
Extended radical Removal of one or more additional
neck dissection lymphatic and/or non-lymphatic
structures(s) relative to a RND, e.g.
level VII, retropharyngeal lymph
nodes, hypoglossal nerve FIG. 1
Algorithm for management of the N0 neck.
NECK METASTASES IN HEAD AND NECK CANCER: UK GUIDELINES
cent, p < 0.001). A meta-analysis of all previously
published RCTs including data on 283 patients
showed that elective neck dissection reduced the
risk of disease-specific death (fixed-effects model
relative risk = 0.57, 95 per cent CI 0.36–0.89, p =
0.014; random-effects model relative risk = 0.59,
95 per cent CI 0.37–0.96, p = 0.034) compared with
observation.8
The classical RND has no role to play in elective
treatment of the N0 neck.9 The choice lies between an
MRND and an SND. Prospective studies suggest
SND is as effective as MRND for most primary sites
with minimal morbidity. Table IV shows the suggested
neck levels that should be addressed for various primary
sites, with the recommendations based on a recent ana-
lysis of the evidence base.9 For oral cavity tumours,
SND of levels I to III should be performed. Due to
the possibility of skip lesions in level IV, especially in
tongue tumours, some studies recommend including
level IV. In oropharyngeal, laryngeal and hypopharyn-
geal tumours, SND of levels II–IV should be per-
formed. Level IIb dissection may not be necessary for
the majority of patients, as the incidence of isolated
metastasis at this site is less than 2 per cent.10
Elective neck irradiation is as effective as elective neck
dissection in controlling subclinical regional disease,
with control rates reported to be around 90 per cent.
When the primary tumour is treated with RT, first
echelon lymph nodes, which are at the greatest risk of
harbouring occult disease, are usually included in the
high dose or radical RT treatment volume. A large retro-
spective series comparing elective neck dissection and
elective neck irradiation in patients with oral cavity, oro-
pharyngeal and laryngeal cancer reported no statistically
significant difference in local control at five years. In
patients with hypopharyngeal cancers, local control
was significantly better with RT compared with
surgery. The consensus guidelines drawn up by experts
from clinical research organizations within Europe,
Asia, Australia/New Zealand and North America, pub-
lished in 2014, should be followed for delineation of
lymph nodal levels in the node negative neck.11
Large retrospective series have reported on the risk
of contralateral nodal involvement by each anatomic
tumour subsite. As in ipsilateral N0 necks, the contra-
lateral neck should be treated if the estimated risk of
TABLE IV
RECOMMENDED NECK LEVELS TO BE DISSECTED FOR
OCCULT NECK DISEASE BASED ON PRIMARY SITE
Oral cavity I–III including IIb
Oropharynx I–III including IIb; recognise significant chance
of contralateral disease
Supraglottis IIa–III; IIb and IV can be spared. Contralateral
SND not indicated for lateralised tumours
Glottis IIa–III; IIb can be spared. Include IV for T3 and
T4 primaries
Subgottis II–IV, VI
Hypopharynx II–IV
S165
occult spread exceeds 15–20 per cent, as occurs with
tumours encroaching or crossing the midline. Elective
nodal irradiation may be preferred to surgery when
both sides of the neck are to be treated.
In long-term follow-up of the untreated N0 neck,
consideration should be given where available to ultra-
sound surveillance and ultrasound-guided aspiration
cytology as a method of detecting and treating early
disease before it becomes clinically palpable.12
Recurrent primary cancer. Occult metastatic rates are
low (5–10 per cent) in the setting of radiorecurrent
cancer if the neck has been included in the radiation
field. As neck dissection (ND) in the salvage setting
is associated with more complications with no reported
benefit, if access to the neck vessels is not needed for
primary resection or reconstruction, routine elective
neck dissection may not be needed during salvage
surgery for locally recurrent primary cancers.
Recommendations
• Patients with a clinically N0 neck, with more
than 15–20 per cent risk of occult nodal
metastases, should be offered prophylactic
treatment of the neck (R)
• The treatment choice of the N0 neck should be
guided by the treatment to the primary site (G)
• If observation is planned for the N0 neck, this
should be supplemented by regular
ultrasonograms to ensure early detection (R)
• All patients with T1 and T2 oral cavity cancer
and N0 neck should receive prophylactic neck
treatment (R)
• Selective neck dissection is effective as MRND
for controlling regional disease in N0 necks
for all primary sites (R)
• Elective neck dissection and elective neck
irradiation have equal efficacy in controlling
occult neck disease (R)
Management of the clinically node positive neck
When there is clinical or radiological evidence of
disease in neck lymph nodes, active treatment is
required. Level 1 studies exist to guide the treatment
of metastatic neck disease in specific scenarios
(Figures 2 and 3). The risk of occult metastases in
other apparently uninvolved levels of the neck is
high, and depending on the primary site, treatment
of these nodes is also required. Level V is least
likely to be involved, with between 3 and 7 per cent
of patients undergoing RND having positive nodes
at level V. The treatment choice of the N+ neck
should be guided by the treatment to the primary
site, and there is long-term data to support this
premise.13
S166 V PALERI, T G URBANO, H MEHANNA et al.

FIG. 2
Algorithm for management of the N+ neck when surgery is the primary modality.

FIG. 3
Algorithm for management of the N+ neck when chemoradiation is the primary modality.

N1 neck disease. Prospective data from large cancer
databases suggest that single modality therapy is suf-
ficient to deal with ipsilateral, single nodes of less
than 3 cm in size. If surgery is the chosen modality,
SND may be appropriate. As approximately 50 per
cent of clinically N1 necks are upstaged after patho-
logical assessment, many patients subsequently
require post-operative radiation. Prospective studies
have shown that in the absence of bulky disease
(N1, N2b), appropriate SND in combination with
NECK METASTASES IN HEAD AND NECK CANCER: UK GUIDELINES
postoperative RT result in neck control rates equiva-
lent to those achieved by comprehensive neck dissec-
tion.9 Complete response rates are much higher in
patients with nodes of less than 3 cm in size and
regional control rates following RT alone are best in
patients with nodes less than 2 cm in size.
N2 and N3 neck disease. If the primary modality is
surgery for this stage of neck disease, MRND and
RND result in equivalent rates of disease control in
the neck when performed in appropriately selected
patients.9 Retrospective and prospective studies
suggest that adding irradiation post-operatively
increases regional control,14 especially in the presence
of adverse features such as extracapsular nodal spread,
positive margins, pT3 or pT4 primary, pN2 or pN3
nodal disease, nodal disease in levels IV or V, peri-
neural invasion and vascular invasion. Randomised
controlled trials from the EORTC and RTOG have
shown improved control with chemoradiotherapy in
the post-operative setting, especially in the presence
of extracapsular spread and/or microscopically
involved surgical margins.15 Patients with two or
more histopathologically involved lymph nodes
without extracapsular spread as their only risk factor
did not benefit from the addition of chemotherapy.
Morbidity of neck irradiation is higher in patients
who have undergone an RND.
If the primary site is suitable for non-surgical treat-
ment, the neck should be treated at the same time. For
neck disease staged N2 and above, this will usually
involve chemoradiotherapy. The PET-Neck phase III
randomised trial compared PET–CT-guided active
surveillance with planned neck dissection for neck
disease staged N2 or N3 treated by chemoradiother-
apy. The study recruited 282 patients into each arm
and showed that the survival outcomes were similar
with a minimum follow up of two years. A post treat-
ment PET–CT surveillance strategy led to fewer neck
dissections, fewer complications, was cost effective
(per person cost saving of £1415) and provided 0.07
additional quality adjusted life years compared with
planned neck dissection. Based on the results of the
PET-Neck trial, there is no role for planned neck dis-
section after primary chemoradiotherapy.16 The
current standard of care should be a CT–PET scan
between 10 and 12 weeks following chemoradiother-
apy, with ND being offered to those who show incom-
plete or equivocal response of nodal disease.
Complete responders may need no further interven-
tion.17 The extent of the salvage neck dissection can
be based on local protocols, with the recognition
that there is an increasing trend to perform a limited
neck clearance in these individuals, with removal of
the involved level alone or an adjacent level. In
patients with fixed and unresectable nodal disease,
RT or chemoradiotherapy will be the only options
available, but a low likelihood of curative outcome
should be recognised.
S167
If the primary tumour is small but sited where resec-
tion is not feasible, and associated with advanced neck
disease, resection of the nodal disease followed by treat-
ment of the primary tumour by RT (± chemotherapy)
plus post-operative RT to the involved neck could poten-
tially be considered but this will be associated with a sig-
nificant delay in the management of the primary disease
which may result in interval primary disease progression.
Recommendations
• The treatment choice to the N+ neck
should be guided by the treatment to the
primary site (G)
• Selective neck dissection alone is adequate
treatment for pN1 neck disease without
adverse histological features (R)
• Post-operative radiation for adverse histologic
features following SND confers control rates
comparable to more extensive procedures (R)
• Adjuvant radiation following surgery for
patients with adverse histological features
improves regional control rates (R)
• Post-operative chemoradiation improves
regional control in patients with extracapsular
spread and/or microscopically involved
surgical margins (R)
Assessing treatment response
Neck node size and fixity predict response rate and local
control with RT alone. In patients with clinical N2 or N3
disease, there is poor correlation between clinical and
pathological response following chemoradiotherapy. As
discussed above, the PET-Neck trial demonstrated
equivalent survival rates to planned neck dissection,
with a lower morbidity and a higher overall cost-effective-
ness. Co-registered PET–CT scans, performed at least 10
weeks after treatment is now considered the standard of
care. A negative PET–CT scan following treatment por-
tends a high disease free survival.18 High standard uptake
values are associated with residual disease and this can be
used to decide the need for neck dissection following
primary chemoradiotherapy.17,19,20
Recommendations
• Following chemoradiation therapy, complete
responders who do not show evidence of
active disease on co-registered PET–CT scans
performed at 10–12 weeks, do not need
salvage neck dissection (R)
• Salvage surgery should be considered for
those with incomplete or equivocal response
of nodal disease on PET–CT (R)
S168
Management of recurrent neck disease
Prior to planning salvage treatment, the patient should be
meticulously evaluated for distant metastases. This
group is likely to benefit from PET–CT scans to look
for distant metastases. If the recurrence has occurred fol-
lowing RT or chemoradiotherapy and is surgically
resectable, surgery should be offered but acknowledge
the higher risk of complications. In patients who
present with unresectable disease, re-irradiation with or
without chemotherapy should be considered, particular-
ly in those who present more than two years since their
previous treatment. Evidence of partial repair of RT-
induced spinal cord subclinical damage and newer RT
delivery techniques (IMRT, Tomotherapy®, protons)
that allow better sparing of neurological, vascular and
soft tissue at risk make this a realistic option in a
larger number of patients. In patients who recur after pre-
vious surgical treatment, options include re-resection
followed by adjuvant radiation, or primary RT or
chemoradiotherapy.
Palliative care
Patients who have incurable nodal recurrence present a
significant challenge, particularly when distant metas-
tases are not present as people can then live with recur-
rent disease for many months or longer. Fungating
neck nodes have a significant effect on psychosocial
function. The impact on speech and swallowing
needs careful discussion with dieticians and speech
and language therapists so that the potential benefits
of tube feeding can be weighed against the risk of
over-medicalising terminal care. Specialist palliative
care teams should ideally be involved in these discus-
sions before such complications develop.
There may be occasions where palliative RT, chemo-
therapy or surgery have the potential to improve quality
of life (QoL) in this situation. The overall expected
prognosis, patient perspective and goals, morbidity of
treatment and likely benefits need to be openly dis-
cussed to ensure that there is a reasonable expectation
that any intervention will improve QoL for a given
individual.
Ongoing research
Current portfolio studies open to recruitment and rele-
vant to neck metastases include: the role of SND in
patients with early oral SCC (1–3 cm primary size)
and no clinical evidence of lymph node metastases in
the neck (SEND trial).
Key points
• The neck stage is the single most important
tumour prognostic factor
• Prognosis is affected by number of involved
nodes, the anatomic level in the neck, tumour
load, the presence of extracapsular spread, peri-
neural and vascular invasion, previous treatment
by surgery or radiotherapy and resectability
V PALERI, T G URBANO, H MEHANNA et al.
• A large number of malignant nodes will measure
less than 10 mm in diameter and extracapsular
spread will occur in a substantial percentage of
smaller nodes, as small as 2 mm. These may not
be identified on conventional (CT and magnetic
resonance) imaging
• Incidence of nodal metastases depends on site and
size of the primary tumour. This figure may be as
low as 1 per cent for early glottic tumours or as
high as 80 per cent for nasopharyngeal carcinomas
• The majority of tumours will metastasise in a pre-
dictable manner to certain nodal groups but it
should be remembered that tumours can metasta-
sise to more remote sites (i.e. nasopharyngeal
cancers to level V, tongue cancers to level IV)
and that the pattern of spread will be disrupted
by previous surgery or radiotherapy
• The possibility of bilateral nodal disease should be
considered especially when the primary site
involves the tongue base, nasopharynx or supra-
glottic larynx or when the primary site crosses
midline
• Neck dissections should be documented as per the
accepted classification system
• Radiotherapy target delineation should follow the
internationally recognised consensus guidelines
• Standardised reporting of neck dissection speci-
mens according to the Royal College of
Pathologists data set is essential
• Issues of function and quality of life have to be
considered in the management of metastatic neck
disease.
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added to locoregional treatment for head and neck squamous-
cell carcinoma: three meta-analyses of updated individual data.
MACH-NC collaborative group. Meta-analysis of chemotherapy
on head and neck cancer. Lancet 2000;355:949–55
15 Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J,
Forastiere A et al. Defining risk levels in locally advanced
head and neck cancers: a comparative analysis of concurrent
postoperative radiation plus chemotherapy trials of the
EORTC (#22931) and RTOG (# 9501). Head Neck 2005;27:
843–50
S169
16 Mehanna HM, Wong WL, McConkey CC, Rahman JK,
Robinson M, Hartley AGJ et al. PET-NECK – a multi-centre
randomized phase III controlled trial (RCT) comparing
PETCT guided active surveillance with planned neck dissection
(ND) for locally advanced (N2/N3) nodal metastases (LANM)
in patients with head and neck squamous cell cancer (HNSCC)
treated with primary radical chemoradiotherapy (CRT). N Engl J
Med 2016;374:1444–54
17 Gupta T, Master Z, Kannan S, Agarwal JP, Ghsoh-Laskar S,
Rangarajan V et al. Diagnostic performance of post-treatment
FDG PET or FDG PET/CT imaging in head and neck cancer:
a systematic review and meta-analysis. Eur J Nucl Med Mol
Imaging 2011;38:2083–95
18 Sjovall J, Chua B, Pryor D, Burmeister E, Foote MC, Panizza B
et al. Long-term results of positron emission tomography-direc-
ted management of the neck in node-positive head and neck
cancer after organ preservation therapy. Oral Oncol 2015;51:
260–6
19 Wee JT, Anderson BO, Corry J, D’Cruz A, Soo KC, Qian CN
et al. Management of the neck after chemoradiotherapy for
head and neck cancers in Asia: consensus statement from the
Asian Oncology Summit 2009. Lancet Oncol 2009;10:1086–92
20 Isles MG, McConkey C, Mehanna HM. A systematic review and
meta-analysis of the role of positron emission tomography in the
follow up of head and neck squamous cell carcinoma following
radiotherapy or chemoradiotherapy. Clin Otolaryngol 2008;33:
210–22
Address for correspondence:
Vinidh Paleri,
Department of Otolaryngology – Head and Neck Surgery,
The Newcastle upon Tyne Hospitals NHS Foundation Trust,
Northern Institute of Cancer Research,
Newcastle upon Tyne, UK
E-mail: vinidh.paleri@ncl.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S170–S175. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000591

Investigation and management of the unknown

primary with metastatic neck disease: United
Kingdom National Multidisciplinary Guidelines

K MACKENZIE1, M WATSON2, P JANKOWSKA3, S BHIDE4, R SIMO5

1
University of Strathclyde, Glasgow, 2ENT Department, Doncaster Royal Infirmary, Doncaster, 3Department of
Oncology, Beacon Centre, Taunton and Somerset NHS Foundation Trust, Taunton, 4Head and Neck Unit,
The Royal Marsden NHS Foundation Trust, London, and 5Department of Otolaryngology – Head and Neck
Surgery, Guy’s and St Thomas’ Hospital NHS Foundation Trust, Department of Otolaryngology – Head and Neck
Surgery, Guy’s, King’s and St Thomas’ Medical and Dental School, London, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. It discusses the evidence base pertaining to the management of metastatic neck disease in
the setting of an unknown primary and provides recommendations on the work up and management for this
group of patients receiving cancer care.
Recommendations
• All patients presenting with confirmed cervical lymph node metastatic squamous cell carcinoma and no apparent primary
site should undergo:
○ Positron emission tomography-computed tomography whole-body scan. (R)
○ Panendoscopy and directed biopsies. (R)
○ Bilateral tonsillectomy. (R)
• Tongue base mucosectomy can be offered if facilities and expertise exists. (G)
• Concomitant chemotherapy with radiation should be considered in patients with an unknown primary. (R)
• Concomitant chemotherapy with radiation should be offered to suitable patients in the post-operative setting, where indi-
cated. (R)
• Neo-adjuvant chemotherapy can be used in gross ‘unresectable’ disease. (R)
• Patients should be followed up at least two months in the first two years and three to six months in the subsequent years. (G)
• Patients should be followed up to a minimum of five years with a prolonged follow up for selected patients. (G)
• Positron emission tomography–computed tomography scan at three to four months after treatment is a useful follow-up
strategy for patients treated by chemoradiation therapy. (R)

Introduction or multiple lumps. The lumps are usually located in

An unknown primary is defined as a squamous cell car-
cinoma (SCC) presenting in a lymph node or nodes in
the neck with no primary index site in the head and
neck having been identified. These patients are best
assessed comprehensively through a dedicated neck
lump clinic. As part of this assessment the lymph
node should be sampled and in general it is recognised
that this is best achieved by ultrasound-guided fine
needle aspiration (FNA) cytology and/or core biopsy
under ultrasound guidance. The receipt of a cytological
or histological report confirming SCC initiates the need
for further investigation.
Clinical presentation
Neck lumps presenting with no discernible primaries
can be solid or cystic lesions, which can be solitary
level 2, followed by level 3, with bilateral involvement
and other symptoms (i.e. pain and dysphagia) reported
in less than 10 per cent. The clinical N stage at presen-
tation is usually N2a, N2b and N2c.1 The presence of
cystic malignant metastases in level 2 is often consid-
ered to be a hallmark of human papilloma virus
(HPV)-related squamous carcinoma, usually with sub-
clinical primaries in the oropharynx.1 The first echelon
lymph node or nodes, which are involved in SCC can
act as an indicator for the potential origin of the
index primary are shown in Table I.
It should be also noted that patients presenting with
supraclavicular lymphadenopathy may represent a dif-
ferent clinical entity,2 due to the potential for associ-
ation with infraclavicular neoplasms, such as lung
cancer.
INVESTIGATION AND MANAGEMENT OF THE UNKNOWN METASTATIC NECK DISEASE: UK GUIDELINES
TABLE I
FIRST ECHELON LYMPH NODES FOR VARIOUS
PRIMARY SITES
Level 1 Oral cavity, oropharynx
Level 2 Oral cavity, oropharynx, larynx, nose, hypopharynx,
parotid, nasopharynx
Level 3 Oral cavity, oropharynx, larynx, hypopharynx, thyroid,
nasopharynx
Level 4 Larynx, thyroid, hypopharynx, oesophagus
Level 5 Nasopharynx, hypopharynx, thyroid, oropharynx
Level 6 Thyroid, larynx, hypopharynx, cervical oesophagus
Assessment and staging
Clinical examination of the nose, post-nasal space, oral
cavity, oropharynx, larynx and hypopharynx, including
palpation of the oral cavity and tongue base should be
carried out under direct vision and using rigid and flex-
ible endoscopes as appropriate. The skin and scalp of
the head and neck region should be examined to
ensure that there are no significant cutaneous lesions.
If there is an obvious lesion, or high suspicion of a
lesion, then further management in the form of
imaging and panendoscopy of that sub-site should be
carried out. If there is no obvious or highly suspicious
lesion on out-patient assessment, then the patient
should be regarded as having an unknown primary
and should be evaluated further, this clinical entity
being known as a ‘clinical’ unknown primary. To try
to determine the site of the primary the following inves-
tigations and findings should be collated.
Pathology of lymph nodes
The advantage of a core biopsy over FNA cytology is
that a clearer histological picture can be determined.3
Although this is generally used to differentiate
between squamous, thyroid, salivary, breast or bron-
chial origins, it may be possible from the cell architec-
ture to suggest the potential origin of the index primary.
Even though immuno-histochemical techniques may
not be able to suggest the tumour origin they may,
however, potentially exclude sites, e.g. by the use of
lung or thyroid markers. More specific investigations
such as identification of Epstein-Barr virus (EBV)
may correlate highly with a nasopharyngeal site.
Human papilloma virus is a significant aetiological
factor in oropharyngeal cancer and so the identification
of HPV 16 and 18 in a lymph node sample would be
strongly suggestive of an oropharyngeal origin.1,4 P16
positivity is highly predictive of HPV overexpression
and may be used as a surrogate marker to indicate the
HPV status.
Cross-sectional imaging
All patients should have computed tomography (CT)
imaging from skull base to diaphragm as part of the
assessment of a newly diagnosed SCC of the head
and neck.1 In the clinical scenario of an unknown
primary, it would be appropriate to undertake this as
it would assess and confirm the extent of the
S171
lymphadenopathy and whether there is a second
primary or metastasis in the lung. Computed tomog-
raphy imaging may show evidence of a potential
index primary site, although in general, it is infrequent-
ly of significant value in diagnosing low-volume
tumours in the head and neck. If the disease presents
in a level 2/3 lymph node magnetic resonance
imaging (MRI) of the oropharynx, and in particular
the tongue base, tonsil and tonsil lingual angle,
should be carried out. It could be argued that all
unknown primary patients should have an MRI of the
neck up to skull base. It should be borne in mind,
however, that positron emission tomography–com-
puted tomography (PET-CT) may be carried out as
the first-line investigation of these patients in which
case ‘plain’ CT should not be carried out.
Positron emission tomography–computed tomography
fusion scan
Positron emission tomography-computed tomography
scanning is the recognised investigation of choice in
the assessment of the unknown primary and has been
shown to be superior to CT scanning alone. Recent
meta-analysis reported an identification rate of 44 per
cent, a sensitivity of 97 per cent and a specificity of
68 per cent.5,6 The evidence in support of this modality
is level 3 and is based on observational series. Within
this assessment it should be noted that there is a signifi-
cant false-positive identification rate associated with
PET–CT scan. Despite these limitations, PET–CT
has now been confirmed as not only the imaging
modality of choice in the investigation of an
unknown primary, but is now also regarded as the
current standard of care.1
Panendoscopy
Following each of the clinical and radiological assess-
ments it is necessary to carry out panendoscopy of the
upper aerodigestive tract under general anaesthesia.
The timing of this should be following the comple-
tion of all of the imaging as any instrumentation and
biopsy of these areas prior to scanning would com-
promise the accuracy of the subsequent radiological
assessments. In addition, imaging may identify a
potential primary site for a targeted biopsy.
Under general anaesthesia, each of the subsites of the
head and neck should be examined under direct vision
and by use of all types of straight and angled telescopes
appropriate to that area. The subsites which should be
examined are the nose, paranasal sinuses, nasopharynx,
oral cavity, hard and soft palates, tongue base, tonsil,
posterior pharyngeal wall, vallecula, supraglottis,
glottis, subglottis, pyriform fossa, post-cricoid region
and proximal oesophagus. Palpation of oral cavity
and tongue base should also be carried out.
In any of these areas if there is any suspicion of
ulceration, change in colour, asymmetry or fullness,
then the area should be photographed and appropriate
deep biopsies taken. If there is no obvious lesion,
S172
then the question of random biopsies arises. Although
there is little evidence in support of this long-standing
practice, biopsy of the post-nasal space, tongue base
and/or pyriform fossa would still appear to be
common practice especially if the positive lymph
node is one of the first echelon lymph nodes draining
the index site being biopsied.
There is an evolving evidence base in support of ever
increasing oropharyngeal lymphoid tissue resection. It is
now accepted that bilateral tonsillectomy should be
carried out. An extension of this principle is an increas-
ing body of evidence in support of excision or sampling
the lingual tonsil (tongue base mucosectomy),7–9 which
is best accomplished by transoral robotic surgery.10,11
Although this increases the yield of squamous carcin-
oma primaries the effect that this might have on structure
and function within the oropharynx and ultimately how
it relates to survival needs clarification.
Most current groups would suggest that PET–CT
imaging, in conjunction with panendoscopy, directed
biopsy as appropriate and bilateral tonsillectomy offer
the greatest chance of identifying the occult primary
tumour in the routine clinical setting. The role of
tongue base mucosectomy by transoral laser or
robotic approach, with or without PET–CT or HPV
positivity needs prospective evaluation.
Following detailed clinical, radiological and opera-
tive assessment, if an index primary site is identified
then treatment should be according to the guidelines
for that site with nodal metastasis. If each of these
investigations is negative, then this should be regarded
as a ‘true’ unknown primary and the treatment consid-
ered as such.
Staging
The neck is staged as set out elsewhere in this supple-
ment. It should be noted that the correct T stage for an
unknown primary is T0 and not TX.
Treatment
The aim of the treatment of the majority of patients
with a ‘true’ unknown primary tumour in the head
and neck should be curative with the least morbidity
to the upper aerodigestive tract possible. The treatment
of an occult mucosal primary is often assumed and
based on the well-studied natural history of mucosal
squamous cell cancers of the upper aerodigestive
tract. Most treatment regimens will therefore involve
combined modality treatment, but on occasions, radio-
therapy (RT), and even more rarely surgery, will be
used as single modality treatment.12 The rate of emer-
gence of the primary tumour is approximately 3 per
cent per year, which is equivalent to the development
of second carcinomas in the head and neck, lung and
oesophagus. Therefore the primary aim of treatment
is locoregional control. However, the rarity of
unknown primaries (approximately 1–2 per cent of
all squamous head and neck cancers) means there is a
dearth of literature to guide best practice. Many of the
K MACKENZIE, M WATSON, P JANKOWSKA et al.
management decisions are therefore controversial,
and based on individual centre case series.
Recommendations
• All patients presenting with confirmed
cervical lymph node metastatic SCC and no
apparent primary site should undergo:
• Positron emission tomography–computed
tomography whole-body scan (R)
• Panendoscopy and directed biopsies (R)
• Bilateral tonsillectomy (R)
• Tongue base mucosectomy can be offered if
facilities and expertise exist (G)
Surgery on its own may be sufficient treatment for N1
necks demonstrating no extracapsular spread, but in all
other scenarios, needs to be supplemented by adjuvant
(chemo) radiation (Table II).
For more advanced neck disease intensive combined
treatment is required. This could be either a combin-
ation of neck dissection and RT or initial (chemo)-
radiotherapy followed by planned neck dissection if a
complete response is not evident on imaging. Both of
these approaches appear to be equally effective. Of
emerging significance is the question of HPV 16 and
18 positivity and the effect it has on treatment recom-
mendations. Given the apparent good clinical response
to HPV-positive lymph nodes then the question arises
as to the advisability of surgical clearance of the neck
with or without adjuvant (chemo) radiotherapy or
whether primary RT should be considered as the only
treatment modality in this specific group.
Surgery
T0N1
T0N1 – no extracapsular spread. Patients presenting
with N1 disease and who are subsequently confirmed
following surgery as having pN1 disease without extra-
capsular spread may be treated with surgery alone pro-
vided the surgery has been comprehensive. This should
be in the form of a modified radical neck dissection
(MRND), including levels 1–5, and in the vast majority
preserving the ipsilateral sternomastoid muscle, intern-
al jugular vein and accessory nerve. This has been
shown to be as effective as RT and clearly avoids the
potential side effects of RT. There are no randomised
data to support MRND over selective neck dissection
(SND).13 However, in the absence of other adjunctive
therapies for the N1 neck, a MRND may be preferred
as its extent and subsequent radiological assessment
may avoid the need for radiation.
T0N1 – with extracapsular spread. When extracapsular
spread is found, however, then RT to at least the
involved nodal levels is necessary, although it is more
usual to irradiate the entire ipsilateral post-operative
INVESTIGATION AND MANAGEMENT OF THE UNKNOWN METASTATIC NECK DISEASE: UK GUIDELINES
TABLE II
TREATMENT RECOMMENDATIONS
Stage Surgery
T0N1 (no ECS) SND or MRND
T0N1 (ECS) SND or MRND
T0N2a, N2b, N2c SND or MRND±contralateral
SND or MRND
T0N3 Radical or type I MRND
SND = selective neck dissection; MRND = modified radical neck dissection
neck, and boost the involved levels. The addition of
chemotherapy to RT for occult primary head and neck
cancer has not yet been established. However, as post-
operative chemoradiation has been demonstrated to be
superior to post-operative radiation alone in the context
of pathologically confirmed extracapsular spread, in
patients with detectable upper aerodigestive tract
cancers, the addition of concomitant platinum-based
chemotherapy to radiation should be considered.14
There are no robust data to support the additional use
of total mucosal irradiation (TMI) with ipsilateral neck
radiation following neck dissection for T0pN1 disease.
There are also some reports that locoregional tumour
control is up to 40 per cent higher with surgery and
radiation therapy compared with radiation alone,
meaning radiation alone, even for N1 disease, must
remain an option only for those who are inoperable
on medical grounds or where it is considered appropri-
ate for those who are HPV positive.
T0N2a, T0N2b and T0N2c
For each of these stages comprehensive clearance of the
involved lymph node levels is usually required in the
form of MRND or SND with possible contralateral
SND or MRND. The rate of regional recurrence for
SND is similar to reported rates for MRND, when com-
bined with adjuvant radiation, such that SND may be
an appropriate surgical option for more advanced
neck disease in selected patients. Equally in less
advanced disease it has been reported that SND can
be used with similar efficacy to MRND. Radical RT
to one or both sides of the neck should be considered,
even for pN2a disease, as in one of the largest series of
occult primary head and neck cancer in 136 patients
from the MD Anderson Centre, combined surgery
and post-operative radiation was associated with
lower rates of locoregional relapse and higher
disease-free survival. This radiation may be given
with or without concomitant chemotherapy as
described above. While there remains no randomised
data to support the use of chemotherapy for pN2
disease from an occult head and neck primary, there
are two case series both demonstrating excellent pro-
gression-free survival (PFS) and overall survival (OS)
rates. The chemotherapy protocols used were heteroge-
neous, and included concomitant cisplatin, concomi-
tant 5-fluorouracil (5-FU) and hydroxyurea, as well
as paclitaxel.
S173
Radiotherapy Chemotherapy
No unless for mucosal sites No
Yes – either involved lymph nodes or ipsilateral Should be considered
neck and boost to involved lymph nodes
Yes – ipsilateral but bilateral should be considered Should be considered
Yes – ipsilateral but bilateral should be considered Should be considered
In the absence of supportive data, radiation of poten-
tial index sites, depending on the lymph nodes levels
involved, remains controversial. It should remain an
area of active investigation, with the conventional man-
agement of patients with pN2 disease being as described
above.
T0N3
It may not be possible to have a curative aim in patients
with this staging. There is, however, a potential role for
surgery as palliation, in the form of a radical neck dissec-
tion with the aim of preventing or delaying, the onset
of fungation of the nodal metastasis. For curative intent
a radical neck dissection or Type I MRND with post-
operative chemoradiotherapy will usually be necessary.
Radiotherapy
Primary treatment. For N1 disease with extracapsular
spread, N2 and N3 disease, initial chemoradiation
with planned neck dissection only for those patients
not achieving a clinical or metabolic complete response
on post-treatment imaging is a valid management strat-
egy.12,15 The extent of the RT fields to be treated is
controversial. In the absence of high-level evidence,
the practice of radiation therapy in this setting includes
involved field only or bilateral neck and TMI. The latter
is practiced commonly in the UK.
Adjuvant treatment. There is a lack of consensus on the
RT target volumes that should be treated after neck dis-
section.16 Treatment of the ipsilateral hemi-neck alone
is of considerably lower toxicity and has been shown to
achieve local control rates in the cervical nodes of 90
per cent with contralateral relapse rates as low as 4.7
per cent, provided treatment strategies are determined
using PET–CT. However, total mucosal and bilateral
neck irradiation of the head and neck region is a
common practice with the aim of eradicating the
primary and the microscopic neck disease.
With the addition of cisplatin to primary RT for the
treatment of head and neck cancer, an absolute
survival benefit of 6.5 per cent is seen at five years.
Investigating concomitant chemoradiation in the post-
operative setting, the Radiation Therapy Oncology
Group (RTOG) demonstrated a 10 per cent improvement
in locoregional control rate, and a 22 per cent risk reduc-
tion of disease recurrence and death at two years, while
the European Organisation for Research and Treatment
S174
of Cancer (EORTC) group showed a 13 per cent improve-
ment in locoregional control, 25 per cent risk reduction of
disease progression, and 30 per cent risk reduction of
death at five years.14,17 These findings were based on
the concomitant use of cisplatin 100 mg/m2 on days 1,
22 and 43, which must therefore remain the gold standard.
Total mucosal irradiation. This remains a controversial
issue. In the largest series to date, no patient developed
a metachronous primary in the follow-up period, and so
would have experienced only toxicity rather than
benefit from TMI. Some groups have recommended
bilateral neck and TMI for occult primary head and
neck cancer patients, claiming improved local control,
but no OS benefit. There is no conclusive evidence to
support the routine use of TMI.
What is clear, however, is that with conventional RT
techniques, TMI is given at the price of significant
acute toxicity and chronic morbidity, mainly xerosto-
mia with its associated complications and effects on
quality of life. Intensity modulated radiation therapy
(IMRT) enables delivery of different doses during
TMI, thus potentially reducing treatment related tox-
icity. Four centres have reported their experience of
using IMRT to deliver TMI for unknown primaries,
with excellent two-year locoregional control (85–88
per cent) and OS (74–85 per cent). The MD
Anderson group, however, has most recently reported
the most mature data, with five-year actuarial locore-
gional control of 94 per cent and OS of 89 per cent.18
The TMI in all reports was well tolerated, and with sig-
nificantly reduced xerostomia and mucositis. Due to
the lack of randomised evidence, the post-operative
RT volume treated should therefore be at the discretion
of the treating clinician. If TMI is advocated the use of
IMRT is recommended.19,20
Radiation dosage schedules:
• Post-operative neck: 60 Gy in 30 fractions or
equivalent
• Post-operative neck with extracapsular spread:
64–66 Gy in 32–33 fractions or equivalent
• Gross macroscopic disease still present: 70 Gy in
30 fractions or equivalent
• Putative mucosal sites and the uninvolved neck:
50 Gy in 25 fractions or equivalent.
Chemotherapy
In the absence of randomised data to support chemo-
therapy, either before, during or after radiation for
occult primary head and neck cancer, the indications
for chemotherapy with post-operative or radical RT
should be as for treatment of patients with detectable
head and neck SCCs. The chemotherapy regimen
used is at the discretion of the treating clinician, but
will usually be platinum-based, single-agent cisplatin
or carboplatin or cetuximab in patients with suboptimal
renal function.
K MACKENZIE, M WATSON, P JANKOWSKA et al.
Recommendations
• Concomitant chemotherapy with radiation
should be considered in patients with an
unknown primary (R)
• Concomitant chemotherapy with radiation
should be offered to suitable patients in the
post-operative setting, where indicated (R)
• Neo-adjuvant chemotherapy can be used in
gross ‘unresectable’ disease (R)
Neo-adjuvant chemotherapy. While the meta-analysis
of chemotherapy in head and neck cancer (MACH-
NC) failed to demonstrate a significant benefit for
the use of induction chemotherapy,21 many of the his-
torical trials included pre-dated the use of taxanes.
Both the EORTC 24971 and TAX 323 studies and
the TAX 324 trial found that the addition of docetaxel
(T) to cisplatin (P) and 5-FU resulted in improved
PFS, OS and response rate and yet lower associated
toxicity. In the context of gross unresectable neck
disease, it therefore seems reasonable to consider the
use of such induction chemotherapy, particularly for
patients with excellent performance status, as a cyto-
reductive measure prior to definitive concomitant che-
moradiation, even for occult primary disease. The
caveat remains that the outcome of such case series
should be reported in the literature where possible,
for this rare group.
Concomitant chemotherapy. The addition of post-opera-
tive adjuvant chemotherapy concurrently with radiation
has transformed with the publication of two trials from
EORTC and RTOG. See section ‘Adjuvant treatment’
for detailed discussion.
Adjuvant chemotherapy. There are no convincing data
that chemotherapy given after radiation or surgery is
of benefit in terms of either disease-free or OS for
patients with detectable primaries. This approach
cannot therefore be recommended for patients with
occult primary head and neck cancer.
Recommendations
• Patients should be followed up at least two
months in the first two years and three to six
months in the subsequent years (G)
• Patients should be followed up to a minimum
of five years with a prolonged follow-up for
selected patients (G)
• Positron emission tomography–computed
tomography scan at three to four months after
treatment is a useful follow-up strategy for
patients treated by chemoradiation therapy (R)
INVESTIGATION AND MANAGEMENT OF THE UNKNOWN METASTATIC NECK DISEASE: UK GUIDELINES
Follow-up
Follow-up schedules should be in keeping with the
monitoring of all patients who have received treatment
for low-volume head and neck SCC with cervical
metastasis, as discussed elsewhere in these guidelines.
The highest risk period for relapse of squamous carcin-
oma following treatment occurs in the first two years. A
frequent follow-up programme of monitoring every 4
weeks up to 18 months is indicated for patients who
have received radical treatment. This should identify
the appearance of a primary, or any recurrence, in
turn allowing their prompt and optimal management.
As previously discussed, PET–CT is frequently a
standard part of the work up for patients presenting
with cervical metastasis from an occult primary. There
are data to suggest that it also plays a useful role in
follow-up. A negative PET–CT scan after treatment
with chemoradiotherapy is associated with a high nega-
tive predictive value (>95 per cent), and a negative scan
undertaken three to four months after completion of
therapy can therefore provide some reassurance for the
patient and clinician that there is no residual disease.
However, there are no data on the value of subsequent
imaging to monitor either subclinical locoregional recur-
rence or the development of a primary cancer, at a later
stage. The decision regarding subsequent imaging,
whether annually or otherwise, remains therefore at the
discretion of the treating clinician.
Key points
• All patients with a clinical unknown primary
should have comprehensive imaging, including
positron emission tomography–computed tomog-
raphy imaging, followed by panendoscopy and
bilateral tonsillectomy
• In the majority of cases, radical treatment should
include surgical clearance of the neck followed
by chemoradiotherapy
• Primary concurrent chemoradiation with planned
neck dissection or neck salvage based on response
is a valid alternative treatment strategy
• If total mucosal irradiation is to be considered,
then intensity modulated radiation therapy
should be used
• Follow-up should be similar to that employed in
patients who have received the treatment for an
identified tumour of the head and neck.
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site: a meta-analysis. Surg Oncol 2013;22:190–94
7 Karni RJ, Rich JT, Sinha P, Haughey BH. Transoral laser micro-
surgery: a new approach for unknown primaries of the head and
neck. Laryngoscope 2011;121:1194–201
8 Graboyes EM, Sinha P, Thorstad WL, Rich JT, Haughey BH.
Management of human papillomavirus-related unknown primar-
ies of the head and neck with a transoral surgical approach. Head
Neck 2015;37:1603–11
9 Nagel TH, Hinni ML, Hayden RE, Lott DG. Transoral laser
microsurgery for the unknown primary: role for lingual tonsil-
lectomy. Head Neck 2014;36:942–6
10 Durmus K, Patwa HS, Gokozan HN, Kucur C, Teknos TN,
Agrawal A et al. Functional and quality-of-life outcomes of
transoral robotic surgery for carcinoma of unknown primary.
Laryngoscope 2014;124:2089–95
11 Mehta V, Johnson P, Tassler A, Kim S, Ferris RL, Nance M
et al. A new paradigm for the diagnosis and management of
unknown primary tumors of the head and neck: a role for trans-
oral robotic surgery. Laryngoscope 2013;123:146–51
12 Strojan P, Ferlito A, Langendijk JA, Corry J, Woolgar JA,
Rinaldo A et al. Contemporary management of lymph node
metastases from an unknown primary to the neck: II. A review
of therapeutic options. Head Neck 2013;35:286–93
13 Dragan AD, Nixon IJ, Guerrero-Urbano MT, Oakley R, Jeannon
JP, Simo R. Selective neck dissection as a therapeutic option in
management of squamous cell carcinoma of unknown primary.
Eur Arch Otorhinolaryngol 2014;271:1249–56
14 Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre
JL, Greiner RH et al. Postoperative irradiation with or without
concomitant chemotherapy for locally advanced head and
neck cancer. N Engl J Med 2004;350:1945–52
15 Demiroz C, Vainshtein JM, Koukourakis GV, Gutfeld O, Prince
ME, Bradford CR et al. Head and neck squamous cell carcinoma
of unknown primary: neck dissection and radiotherapy or defini-
tive radiotherapy. Head Neck 2014;36:1589–95
16 Daly PE, McArdle O, Armstrong JG, Yau J, Pinto H, Kaplan M
et al. Can we avoid bilateral radiation therapy in head and neck
carcinoma of unknown primary in the PET–CT era? Int J Radiat
Oncol Biol Phys 2012;84:S250
17 Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH,
Saxman SB et al. Postoperative concurrent radiotherapy and
chemotherapy for high-risk squamous-cell carcinoma of the
head and neck. N Engl J Med 2004;350:1937–44
18 Frank SJ, Rosenthal DI, Petsuksiri J, Ang KK, Morrison WH,
Weber RS et al. Intensity-modulated radiotherapy for cervical
node squamous cell carcinoma metastases from unknown head-
and-neck primary site: M. D. Anderson cancer center outcomes
and patterns of failure. Int J Radiat Oncol Biol Phys 2010;78:
1005–10
19 Richards TM, Bhide SA, Miah AB, Schick U, Gujral DM,
Newbold K et al. Phase 2 trial of total mucosal and bilateral
neck intensity modulated radiotherapy in squamous cell cancer
of unknown primary. Eur J Can 2011;47:S559
20 Shoushtari A, Saylor D, Kerr KL, Sheng K, Thomas C, Jameson
M et al. Outcomes of patients with head-and-neck cancer of
unknown primary origin treated with intensity-modulated radio-
therapy. Int J Radiat Oncol Biol Phys 2011;81:e83–91
21 Pignon JP, le Maitre A, Maillard E, Bourhis J, Group M-NC.
Meta-analysis of chemotherapy in head and neck cancer
(MACH-NC): an update on 93 randomised trials and 17 346
patients. Radiother Oncol 2009;92:4–14
Address for correspondence:
K MacKenzie,
Glasgow Royal Infirmary,
University of Glasgow,
Glasgow, UK
E-mail: Kenneth.MacKenzie@glasgow.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S176–S180. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000608

Speech and swallow rehabilitation in head and neck

cancer: United Kingdom National Multidisciplinary
Guidelines

P CLARKE1, K RADFORD2, M COFFEY3, M STEWART4

1
Department of ENT, Charing Cross and Royal Marsden Hospitals, London, 2Sandwell and West Birmingham NHS
Trust, Birmingham, 3Department of Speech and Language Therapy, Head and Neck/Oncology, Charing Cross
Hospital, London, and 4ENT Department, Royal Alexandra Hospital, Paisley, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. The disease itself and the treatment can have far reaching effects on speech and swallow
function, which are consistently prioritised by survivors as an area of concern. This paper provides
recommendations on the assessments and interventions for speech and swallow rehabilitation in this patient
group.

Recommendations
• All multidisciplinary teams should have rehabilitation patient pathways covering all stages of the patient’s
journey including multidisciplinary and pre-treatment clinics. (G)
• Clinicians treating head and neck cancer patients should consult the National Cancer Rehabilitation Pathway for
head and neck cancers. (G)
• All head and neck cancer patients should have a pre-treatment assessment of speech and swallowing. (G)
• A programme of prophylactic exercises and the teaching of swallowing manoeuvres can reduce impairments,
maintain function and enable a speedier recovery. (R)
• Continued speech and language therapist input is important in maintaining voice and safe and effective swallow
function following head and neck cancer treatment. (R)
• Disease recurrence must be ruled out in the management of stricture and/or stenosis. (R)
• Continuous radial expansion balloons offer a safe, effective dilation method with advantages over gum elastic
bougies. (R)
• Site, length and completeness of strictures as well as whether they are in the presence of the larynx or not, need
to be assessed when establishing the likelihood of surgically improved outcome. (G)
• Primary surgical voice restoration should be offered to all patients undergoing laryngectomy. (R)
• Attention to surgical detail and long-term speech and language therapist input is required to optimise speech
and swallowing after laryngectomy. (G)
• Patients should commence wearing heat and moisture exchange devices as soon as possible after
laryngectomy. (R)

Introduction relevant intervention from dietetics, physiotherapy,

Most head and neck cancers and their treatments affect
speech and swallowing and this section therefore con-
centrates on the rehabilitation of these functions.1–6
Allied health professional (AHP) head and neck
cancer rehabilitation pathways are required as part of
the implementation of the Improving Outlines
Guidance rehabilitation measures and are required for
peer review. These pathways should cover all stages of
the patient’s journey from diagnosis, through treatment,
to survivorship and end of life care and should include
occupational therapy and speech and language
therapy. Pathways for oral rehabilitation with
input from hygienists, restorative dentists, dental
implantologists, prosthetic technicians should also be
considered.
The stages of the pathways and the allied health pro-
fessional interventions appropriate to each stage are
detailed along with an extensive evidence review in
the National Cancer Rehabilitation Pathway for Head
and Neck Cancers.2
SPEECH AND SWALLOW REHABILITATION IN HEAD AND NECK CANCER: UK GUIDELINES
Responsibility for the rehabilitation of voice, speech
and swallowing rests with the whole multidisciplinary
team (MDT), but is the specific role of the speech
and language therapist within this team. Speech and
language therapists should discuss their role and
outline the need for the patient’s active participation
in therapy to maximise outcomes. The patient’s
family and carers are also involved in this rehabilita-
tion. Within the MDT, the decision on an appropriate
course of treatment should take into account the
effects on functions such as voice, speech and swallow-
ing as well as survival so as to suit each individual’s
preferences and lifestyle.
Recommendations
• All MDTs should have rehabilitation patient
pathways covering all stages of the patient’s
journey including multidisciplinary and pre-
treatment clinics (G)
• Clinicians treating head and neck cancer
patients should consult the National Cancer
Rehabilitation Pathway for Head and Neck
Cancers (G)
Rehabilitation of voice, speech and swallow
Goals of rehabilitation
• Achieve the best possible functional outcome and
quality of life (QoL)
• Identify and carry out interventions which are
most effective for both the specific treatment and
the individual patient at the optimal time
• Provide support and rehabilitation to patients and
their carers.
Assessment
All head and neck cancer patients should have a pre-
treatment assessment of speech and swallowing.1–6
Baseline assessments should be undertaken by the
speech and language therapist and appropriate interven-
tions to maintain functions before treatment should be
undertaken. Assessments of voice, speech and swal-
lowing should be carried out at all stages of the
pathway.
Clinical assessments include: oral-motor examin-
ation (lip closure, range of motion), articulation,
tongue control and strength; evaluation of the oropha-
ryngeal swallow (timing, efficiency, aspiration,
tongue and laryngeal motion) and perceptual evalu-
ation of voice quality.
Instrumental assessments of swallowing include flex-
ible endoscopic examination of swallowing, videofluoro-
scopy and/or modified barium swallow.5 Instrumental
assessments of voice include: endoscopy, stroboscopy
S177
and speech studio/laryngograph. These assessments
can provide useful biofeedback to patients and demon-
strate the effectiveness of interventions.
Therapy/interventions
Pre-treatment. Pre-treatment counselling by AHP
teams should be provided to advise on the anticipated
effects of the cancer as well as subsequent treatments
(chemoradiation, radiotherapy (RT), surgery and
palliation).7
A strict programme of prophylactic exercises
and the teaching of swallowing manoeuvres can
reduce specific impairments, maintain functions
and enable a speedier recovery ensuring post-treat-
ment rehabilitation is more successful.8 For those
undergoing surgery the teaching of swallow strat-
egies beforehand can reduce risk and maximise func-
tion. This may also reduce the need for tube feeding
during treatment and the length of post-treatment
tube feeding.
Post-treatment
Voice. Specific therapy techniques can be targeted at
projection, pitch, reduction of fatigue, increased adduc-
tion, coordination of respiration, vocal hygiene and
amplification. These are particularly relevant to those
having laser surgery or RT to the larynx.
Speech. For those undergoing oral resections a pro-
gramme of compensations, articulation and intelligibil-
ity can be started once suture lines have healed.
Swallowing. Following instrumental assessment,
interventions should be targeted at specific physio-
logical deficits and volitional control to compensate
for the changes to the anatomy and physiology. This
can reduce the risk of aspiration, malnutrition and
improve QoL. These interventions include:9
• Postures to reduce aspiration, e.g. head turn, chin
tuck
• Manoeuvres, e.g. supraglottic swallow, Mendelsohn.
• Therapeutic exercises, e.g. thermal tactile stimula-
tion, range of motion, shaker
• Diet modifications regarding textures and recom-
mendations on oral or non-oral intake.
Oral rehabilitation. Intra-oral prostheses providing
palatal lift, obturation and augmentation can
improve speech and swallow function after oral
resections and the speech and language therapist
and restorative dental surgeon and/or prosthetic tech-
nician need to work closely together. Radiation-
induced fibrosis can present with trismus. This can
cause pain, difficulty with oral intake, poor oral
hygiene and lack of dental care. Exercises with
tongue depressors or a specific device can increase
mouth opening.
S178
Recommendations
• All head and neck cancer patients should have
a pre-treatment assessment of speech and
swallowing (G)
• A programme of prophylactic exercises and
the teaching of swallowing manoeuvres can
reduce impairments, maintain function and
enable a speedier recovery (R)
• Continued speech and language therapist
input is important in maintaining voice and
safe and effective swallow function following
head and neck cancer treatment (R)
Management of stenosis and stricture
Prevention, assessment and diagnosis
Dysphonia following RT and chemoradiotherapy to the
oro/hypopharynx is multifactorial and difficult to treat.
Xerostomia, loss of tongue base bulk and fibrosis/
reduced function of constrictors all play a part.
Speech and language therapy and AHPs’ input as
above remains of utmost importance, but stenosis and
stricture can also develop.
Stenosis of the (hypo)pharynx and neopharynx is
common following treatment for laryngeal and pharyn-
geal cancer.10,11 After treatment of cervical oesopha-
geal cancer some degree of stenosis is almost
inevitable in this region especially following CRT.6
Reported rates vary from 8 per cent following
primary chemoradiotherapy to 40 per cent or more fol-
lowing salvage surgery after (chemo)radiotherapy, par-
ticularly if preceded by a pharyngocutaneous fistula.10
Additional dysphagia occurs in extended surgery, par-
ticularly with posterior tongue resection and with
extended neck surgery with sacrifice of glossopharyn-
geal and hypoglossal nerves (lesser), and vagus nerve
(major).12,13
No standardised definition exists to help to measure
stenosis rates. Anatomical stenosis might be of greatest
interest to the surgeon, but functional stenosis is
of no less impact and interest to the patient.
Videofluoroscopy, supplemented by axial imaging, is
the tool best able to identify the nature of a stenosis
of the (neo)pharynx and assess the degree of impact
on swallowing. Importantly, barium swallows also
have the capacity to identify a proportion of occult
recurrences masquerading as benign stenosis.
Predictors of stenosis are helpful to surgeons.
Studies have shown that following laryngectomy and
partial pharyngectomy a 3 cm (unstretched) to 8 cm
(stretched) posterior pharyngeal strip is sufficient to
allow normal post-treatment swallow and voice
rehabilitation. Circular/circumferential rather than
linear scars remain more stenosis prone, but no data
exist on the minimum luminal diameter with a circular
P CLARKE, K RADFORD, M COFFEY et al.
scar to allow normal swallowing. Repair of the supra-
hyoid muscles (which include the middle constrictor)
to the thyropharyngeus muscles after laryngectomy
has been advocated and may improve swallow by redu-
cing the size and effect of a pseudoepiglottis as well as
allowing better function of the middle constrictor.
Cricopharyngeal myotomy and horizontal closure of
the pharynx with laryngectomy is generally held to
improve speech and swallow outcomes especially
when performed with primary tracheo-oesophageal
puncture and valve reconstruction for speech rehabilita-
tion. In addition, the relationship between luminal
diameter and the use of peristaltic vs non-peristaltic
flaps have yet to be quantified in maintaining a func-
tional post-operative voice and swallow.
The role of salivary bypass tubes may reduce fistula
rates and hence possible stricture rates, but this needs
further study.
Treatment
This depends on the type (functional vs anatomical,
scar vs recurrence), site and comorbid factors such as
fitness for further reconstructive surgery. Median
feeding tube placement times following all forms of
treatment for head and neck cancer are in the region
of 20–26 weeks, and up to 50 per cent of patients
reconstructed with free or pedicle flaps are tube-feed
dependent at one year post-surgery. Reported rates of
complication with percutaneous endoscopic gastros-
tomy and radiologically inserted gastrostomy tubes
vary considerably with up to 3 per cent mortality
rates reported in some series and 10 per cent significant
complication in others. Clearly the use of different sup-
plemental feeding techniques will depend on local
experience in this respect.
Dilation of isolated short segment strictures remains
a valuable means of controlling symptoms for patients
with poor life expectancy or multiple comorbidities.10
Continuous radial expansion balloons allow dilation
up to 20 mm diameter and may be safer and more
effective than traditional bougies. They can also be uti-
lised without general anaesthesia. It is clear that many
patients require multiple dilations, often without long-
lasting relief of dysphagia.
Sternomastoid flaps can be useful in the non-
irradiated patient, but are less reliable than pectoralis
major, radial forearm flap (RFF), anterolateral thigh
(ALT) and jejunal flaps. Choice of and reasons for
a particular free flap vary depending on familiarity
with the flap and perceptions of function vs cosmesis.
Reported case series for RFF, jejunum or ALT
describe similar complication rates (<5 per cent flap
failure, up to 50 per cent pharyngocutaneous fistula)
and success rates (speech intelligibility and swallow
performance).14
The length and completeness of stenosis are import-
ant factors in advising patients whether significant
improvement can be obtained. Complete stricture of
the hypopharynx post-chemoradiotherapy can be
SPEECH AND SWALLOW REHABILITATION IN HEAD AND NECK CANCER: UK GUIDELINES
improved with total laryngopharyngectomy, but
patients need to be warned that swallowing outcomes
are often poorer in this group than primary pharyngect-
omy patients.
Cricopharyngeal myotomy
Cricopharyngeal myotomy appears to have little value
per se for improvement of dysphagia following surgical
treatment of cancers of the oropharynx.15 In combin-
ation with vocal fold medialisation, where needed,
and laryngeal elevation, better success rates may be
obtained.
Recommendations
• Disease recurrence must be ruled out in the
management of stricture and stenosis (R)
• Continuous radial expansion balloons offer a
safe, effective dilation method with
advantages over gum elastic bougies (R)
• Site, length and completeness of strictures as
well as whether they are in the presence of the
larynx or not, need to be assessed when
establishing the likelihood of surgically
improved outcome (G)
Rehabilitation after laryngectomy
Speech
Laryngectomy results in significant alteration of
anatomy and often complex rehabilitation. A range
of voice prostheses are now available, with Blom
Singer and Provox being the commonly used ones. If
visual, cognitive and fine motor skills are intact, inde-
pendence should be fostered by teaching patients to
self change their voice prostheses. Where appropriate,
‘hands-free’ outer valves should be available for
patients to try. Although surgical voice restoration
techniques dominate, it is important to consider the
use of oesophageal speech and electrolarynges.
Electrolarynges use an external vibratory source and
are either placed in the mouth or against the neck or
cheek to produce sound. Both these methods can
have their place in the rehabilitation process.16
Speech and language therapists with appropriate
training and expertise in the management of the
stoma and tracheo-oesophageal puncture should be
part of all MDTs. The MDT should ensure that there
are procedures to manage out of hours problems such
as loss or aspiration of prosthesis. Patients and local
teams should be aware that if a prosthesis cannot be
replaced the puncture should be kept patent with a
catheter or stent for instance. Speech and language
therapists should be aware of the need for and rationale
behind, amongst others, videoflouroscopy for trouble-
shooting, botulinum toxin, antifungals, management
S179
of leakage through as well as peripheral leakage
around a prosthesis. The Royal College of Speech
and Language Therapists has recently published an
excellent and comprehensive document covering
these topics: ‘Prosthetic Surgical Voice Restoration
(SVR): The role of the speech and language
therapist’.1
Swallow
There has been a growing appreciation in recent
years that swallowing also requires rehabilitation in
laryngectomy patients.16–18 Although laryngectomy
patients should not aspirate unless their voice pros-
thesis is leaking, they may have difficulty swallow-
ing solid foods or take significantly longer than
others to finish meals. It has been suggested that
as many as 42 per cent of laryngectomy patients
have a degree of dysphagia three years post-surgery
with a 72 per cent incidence of self-reported dyspha-
gia. Higher levels of depression and anxiety have
also been documented in laryngectomees who have
dysphagia.19 Videofluoroscopy is one of a number
of swallow evaluation tools used with laryngectomy
patients and can contribute to surgical consideration
of interventions such as botulinum toxin and dilata-
tion to treat dysphagia. Further rehabilitation tools
include the use of exercises to strengthen specific
muscles such as tongue base. Appetite can also be
affected by a significant loss of ability to taste and
smell after laryngectomy. Olfactory rehabilitation
utilising the ‘polite yawn’ has been proposed to
help correct this.
Respiration
Respiration is altered significantly post-laryngectomy
with the patient now breathing through an open neck
stoma bypassing the nasal passages and throat. As a
consequence of this anatomical change, the ability to
filtrate irritants such as dust from the air and to humid-
ify inhaled air is lost. This can result in increased
mucus production and crusting of dried secretions. In
recent years, humidification exchange devices have
been developed to restore humidification and filtration.
Rehabilitation of pulmonary function should be offered
to all laryngectomy patients and should involve educa-
tion about the use of stoma covers and bibs. The pres-
ence of an open neck stoma causes some patients
anxiety and rehabilitation may include such diverse
subjects as advice about maintaining appearance and
showering safely.
The adjustment to life as a laryngectomee can be
significant. Tools such as the EORTC Core Quality
of Life Questionnaire and the University of
Washington Quality of Life Tool, version 4 can be
useful in identifying not only those at risk of psycho-
social problems but also to help plan and focus
rehabilitation.19
S180
Recommendations
• Primary surgical voice restoration should be
offered to all patients undergoing
laryngectomy (R)
• Attention to surgical detail and long-term
speech and language therapist input is
required to optimise speech and swallowing
after laryngectomy (G)
• Patients should commence wearing heat and
moisture exchange devices as soon as possible
after laryngectomy (R)
Key points
• Speech and swallow rehabilitation needs should
be assessed before treatment
• Assessment and appropriate interventions should
take place throughout the patient journey, includ-
ing ongoing after treatment
• Multidisciplinary assessment and management of
swallowing problems is important
• Videoflouroscopy is an important tool in assessing
swallow problems
• Dysphagia caused by pharyngeal stenosis after
chemoradiotherapy can be difficult to correct
and complex cases should be managed by expert
teams.
References
1 Prosthetic Surgical Voice Restoration (SVR): The role of the
speech and language therapist Policy Statement. 2010, Royal
College of Speech and Language Therapists. In: http://www.
rcslt.org/docs/svr_policy_document (accessed 15 November
2015)
2 National Cancer Action Team. DH. Rehabilitation Care Pathway
Head & Neck. 2010. In: http://webarchive.nationalarchives.gov.uk/
20130513211237/http:/www.ncat.nhs.uk/ (accessed 27 April
2016)
3 Logemann JA, Pauloski BR, Rademaker AW, Colangelo LA.
Speech and swallowing rehabilitation for head and neck
cancer patients. Oncology (Williston Park) 1997;11:651–9
4 Logemann JA. Evaluation and Treatment of Swallowing
Disorders, 2nd edn. Austin, Texas: Pro-Ed, 1998
5 Langmore SE. Role of flexible laryngoscopy for evaluating
aspiration. Ann Otol Rhinol Laryngol 1998;107:446
P CLARKE, K RADFORD, M COFFEY et al.
6 Urken ML, Jacobsen AS, Lazarus CL. Comprehensive approach
to restoration of function in patients with radiation induced phar-
yngo-oesophageal stenosis. Report of 31 patients and proposal
of new classification scheme. Head Neck 2012;34:1317–28
7 Carroll WR, Locher JL, Canon CL, Bohannon IA, McColloch
NL, Magnuson JS. Pretreatment swallowing exercises improve
swallow function after chemoradiation. Laryngoscope 2008;
118:39–43
8 Roe JW, Ashforth KM. Prophylactic swallowing exercise for
patients receiving radiotherapy for head and neck cancer. Curr
Opin Otolaryngol Head Neck Surg 2011;19:144–9
9 Pauloski BR. Rehabilitation of dysphagia following head and
neck cancer. Phys Med Rehabil Clin N Am 2008;19:889–928
10 Prisman E, Miles BA, Genden EM. Presentation and manage-
ment of treatment-induced pharyngo-esophageal stricture.
Lancet Oncol 2013;14:380–6
11 Nguyen NP, Smith HJ, Moltz CC, Frank C, Millar C, Dutta S
et al. Prevalence of pharyngeal and esophageal stenosis follow-
ing radiation for head and neck cancer. J Otolaryngol Head
Neck Surg 2008;37:219–24
12 Greven KM, White DR, Browne JD, Williams DW 3rd, McGuirt
WF Sr, D’Agostino RB Jr. Swallowing dysfunction is a
common sequelae after chemoradiation for oropharynx carcin-
oma. Am J Clin Oncol 2008;31:209–12
13 Best SR, Ha PK, Blanco RG, Saunders JR Jr, Zinreich ES,
Levine MA et al. Factors associated with pharyngoesophageal
stricture in patients treated with concurrent chemotherapy and
radiation therapy for oropharyngeal squamous cell carcinoma.
Head Neck 2011;33:1727–34
14 Richmon JD, Samji HA, Deschler DG. National laryngopharyn-
gectomy and reconstructive surgery survey. Laryngoscope 2009;
119:1472–8
15 Jacobs JR, Logemann J, Pajak TF, Pauloski BR, Collins S,
Casiano RR et al. Failure of cricopharyngeal myotomy to
improve dysphagia following head and neck cancer surgery.
Arch Otolaryngol Head Neck Surg 1999;125:942–6
16 Samlan RA, Webster KT. Swallowing and speech therapy after
definitive treatment for laryngeal cancer. Otolaryngol Clin
North Am 2002;35:1115–33
17 Maclean J, Cotton S, Perry S. Post laryngectomy: it’s hard to
swallow. An Australian study of prevalence and self reports of
swallowing function after a total laryngectomy. Dysphagia
2009;24:172–9
18 Ward E, Frisby J, Stephens M. Swallowing outcomes following
laryngectomy and pharyngolaryngectomy. Arch Otolaryngol
Head Neck Surg 2002;128:181–6
19 Woodard TD, Oplatek A, Petruzzelli GJ. Life after total laryn-
gectomy: a measure of long-term survival, function, and
quality of life. Arch Otolaryngol Head Neck Surg 2007;133:
526–32
Address for correspondence:
P Clarke,
Department of ENT,
Charing Cross and Royal Marsden Hospitals,
London, UK
E-mail: Peter.Clarke@imperial.nhs.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S181–S190. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S002221511600061X

Recurrent head and neck cancer: United Kingdom

National Multidisciplinary Guidelines

H MEHANNA1, A KONG2, SK AHMED3

1
Institute of Head and Neck Studies and Education, College of Medical and Dental Sciences, University Hospital
Birmingham, Heart of England NHS Foundation Trust, 2Institute of Head and Neck Studies and Education,
University of Birmingham, and 3University Hospital Birmingham, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. Recurrent cancers present some of the most challenging management issues in head and
neck surgical and oncological practice. This is rendered even more complex by the poor evidence base to
support management options, the substantial implications that treatments can have on the function and quality of
life, and the difficult decision-making considerations for supportive care alone. This paper provides consensus
recommendations on the management of recurrent head and neck cancer.

Recommendations
• Consider baseline and serial scanning with computed tomography and/or magnetic resonance (CT and/or MR)
to detect recurrence in high-risk patients. (R)
• Patients with head and neck cancer recurrence being considered for active curative treatment should undergo
assessment by positron emission tomography combined with computed tomography (PET–CT) scan. (R)
• Patients with recurrence should be assessed systematically by a team experienced in the range of management
options available for recurrence including surgical salvage, re-irradiation, chemotherapy and palliative care. (R)
• Management of patients with laryngeal recurrence should include input from surgeons with experience in
transoral surgery and partial laryngectomy for recurrence. (G)
• Expertise in transoral surgery and partial laryngectomy for recurrence should be concentrated to a few surgeons
within each multidisciplinary teams. (G)
• Transoral or open partial laryngectomy should be offered as definitive treatment modality for highly-selected
patients with recurrent laryngeal cancer. (R)
• Patients with OPC recurrence should have p16 human papilloma virus status assessed. (R)
• Patients with OPC recurrence should be considered for salvage surgical treatment by an experienced team, with
reconstructive expertise input. (G)
• Transoral surgery appears to be an effective alternative to open surgery for the management of OPC recurrence
in carefully selected patients. (R)
• Consider elective selective neck dissections in patients with recurrent primaries with N0 necks, especially in
advanced cases. (R)
• Selective neck dissection (with preservation of nodal levels, especially level V, that are not involved by disease)
in patients with nodal (N+) recurrence appears to be as effective as modified or radical neck dissections. (R)
• Use salivary bypass tubes following salvage laryngectomy. (R)
• Use interposition muscle-only pectoralis major or free flap for suture line reinforcement if performing primary
closure following salvage laryngectomy. (R)
• Use inlaid pedicled or free flap to close wound if there is tension at the anastomosis following laryngectomy. (R)
• Perform secondary puncture in post chemoradiotherapy laryngectomy patients. (R)
• Triple therapy with platinum, cetuximab and 5-fluorouracil (5-FU) appears to provide the best outcomes for the
management of patients with recurrence who have a good performance status and are fit to receive it. If not fit,
then combinations of platinum and cetuximab or platinum and 5-FU may be considered. (R)
• Patients with non-resectable recurrent disease should be offered the opportunity to participate in phases I–III
clinical trials of new therapeutic agents. (R)
• Chemo re-irradiation appears to improve locoregional control, and may have some benefit for overall survival,
at the risk of considerable acute and late toxicity. Benefit must be weighed carefully against risks, and patients
must be counselled appropriately. (R)
• Target volumes should be kept tight and elective nodal irradiation should be avoided. (R)
• Best supportive care should be offered routinely as part of the management package of all patients with
recurrent cancer even in the case of those who are being treated curatively. (R)
S182
Introduction
Traditionally patients with recurrence of head and neck
cancer (HNC) are considered to have poor prognosis.
As a result the majority of these patients are usually
treated with palliative intent or receive best supportive
care.
Recent systematic review of the literature would
suggest, however, that outcomes of the management
of recurrence are not as dire as is widely considered.
For example, the management of laryngeal recurrence
is reported to have good outcomes with rates of up to
71 per cent two-year overall survival.1 A recent meta-
analysis shows that the outcomes of management of
oropharyngeal cancer recurrence appear to have
improved significantly over the last two decades, reach-
ing five-year survival of 50 per cent in patients treated
surgically.2 The latter may be the result of a combin-
ation of better patient selection, improved surgical
care and the role of the human papilloma virus
(HPV) as an aetiological factor.
These improvements in outcomes suggest the need
for re-appraisal of the treatment paradigms of HNC
recurrence, and the development of specific expertise
in the management of recurrence including probably
the concentration of expertise in centralised regional
or super-regional services.
Evaluation of the patient with recurrence
Evaluation and careful selection of patients with recur-
rence is the crux of successful management.3 There are
several steps in the evaluation process of these patients.
History
It is important to elucidate the details of the previous
treatments that the patient has had, including the chron-
ology and duration since previous treatment. It is also
important to identify any toxicity that the patient has
experienced from previous treatments as this may
have a bearing on any new treatments being offered.
The patient’s past medical history, and current morbid-
ities and general health state are important, as these will
help determine whether the patient is fit enough to
receive further curative or palliative active treatments.
A smoking and alcohol intake history should be
taken. This should especially ascertain whether the
patient is currently still smoking or drinking heavily.
Finally, a social history of the patient’s activities of
daily living and their requirements in terms of speech
and mobility, as well as their social support structures
are important in determining their ability to cope with
the demanding treatments that may be required for
the management of the recurrence.
Assessment and staging
Clinical examination. Even under anaesthetic, examin-
ation can be deceiving if relied upon solely. One study
showed a false negative rate of 31 per cent for examin-
ation under anaesthetic (EUA) biopsies in 131 patients
who showed recurrence within six months of EUA.
H MEHANNA, A KONG, SK AHMED
However, following identification of potential recur-
rence by scanning, EUA can help provide more infor-
mation regarding the feasibility of surgical resection
and aid planning. Furthermore, a biopsy can be used
to assess HPV status, which recently has been found
to be of prognostic value in patients with recurrence.4
In the longer term, as personalised medicine develops,
molecular profiling of the recurrent tumour may
provide insights into the most appropriate systemic treat-
ments for that particular tumour.
Performance status and co-morbidities Assessment
of the patient’s overall fitness for anaesthetic and/or
systemic therapy is necessary, as that is likely to be
an important determinant of whether the patient is
able to receive additional treatment in both a curative
and a palliative setting.
Imaging Positron emission tomography combined
with computed tomography (PET–CT) scanning can
be extremely helpful in the assessment of recurrence
as it can identify the areas of local and nodal recur-
rence, and importantly distant metastasis. The negative
predictive value of PET–CT scan is especially high for
recurrence at both the primary site and the neck,
approaching values between 93 and 95 per cent and
94 and 100 per cent respectively.5 A meta-analysis
also showed high sensitivity and specificity for detec-
tion of distant metastasis in patients with recurrent
HNC (0.92 and 0.95 respectively),6 and PET–CT scan-
ning can change the management in 20 per cent of
patients with HNC recurrence. In one study, 24 of
123 patients were identified to have silent recurrence
or metastasis by PET–CT, of which 50 per cent had
thoracic metastasis and 32 per cent had distant metasta-
sis in other sites7.
A single CT scan or magnetic resonance imaging
(MRI) scan has low accuracy for differentiating
between cancer, oedema, and interstitial radiation
fibrosis and necrosis. Additional imaging such as an
MRI or contrast CT scanning may however be import-
ant for planning surgical procedures and outlining
radiotherapy (RT).
Recommendations
• Consider baseline and serial scanning with
CT or MRI to detect recurrence in high risk
patients (R)
• Patients with HNC recurrence being
considered for active curative treatment
should undergo assessment by PET CT scan
(R)
Decision making for treatment
By combining the findings of the patient assessment
process, the following factors need to be considered
to help select cases that are appropriate for curative
treatment.3
RECURRENT HEAD AND NECK CANCER: UK GUIDELINES
• What was the previous disease and what were the
treatments given? A review of the extent and fea-
tures of the previous disease including any poor
prognostic features and involved margins is neces-
sary. Furthermore, it is important to elucidate the
details of the previous treatment including the
levels of neck dissection, the radiotherapy (RT)
fields and doses as well as ascertaining any geo-
graphic misses and the time since treatment.
• Is there any evidence of distant metastasis? This
severely limits the possibility of cure and therefore
affects the choice and aggressiveness of treatments
to be offered.
• Is it a recurrence at the primary site or a second
primary tumour? It is important to ascertain the
extent and the size of the recurrence of the
primary tumour. Recurrence of a previous
tumour has a poorer outcome than a second
primary. Furthermore, recurrences in the orophar-
ynx have significantly poorer outcomes than those
in the larynx.
• Is there recurrence in the neck? What are the extent
and the size of the neck recurrence and is there any
evidence of soft tissue extension or extracapsular
nodal extension by physical examination and on
imaging? The presence of extracapsular extension
without the ability to give additional adjuvant
treatment significantly reduces the chance of
cure and survival.8
• Is there evidence of involvement of the carotid
arteries, brachial plexus and prevertebral
muscles? Involvement of these makes surgical
resection unlikely and curative resection almost
impossible.
• Can the recurrence be excised surgically with no
gross tumour left behind?
• Are there complications and toxicity of previous
treatment evident, including osteoradionecrosis
or dysphagia? If there are, then the addition of
further treatment may result in considerable tox-
icity and quality of life detriment.
• Is it possible to give RT and/or chemotherapy,
taking into account previous treatment, resultant
toxicities and time of last treatment?
• What are the potential functional deficits of the
proposed treatment for the recurrence?
• What is the state of the patient’s reserve, psycho-
logical state, general health and family and
social support? These factors will be important
to consider if the patient is fit and able to
undergo further treatment.
Patient selection criteria
Studies on the outcomes and prognostic factors for the
treatment of head and neck recurrence are generally
retrospective and of poor quality. They have described,
however, several predictors of good outcome which can
be classified under three main themes: patient factors,
treatment factors and tumour factors.
S183
Patient factors
The patient factor predictors of good outcome include
patients who are non-smokers or who have stopped
smoking, have good general heath (ECOG (Eastern
Cooperative Oncology Group) status 0–1) and
minimal comorbidities,9 a good psychological state,
good family support, those who are married, and
those who are religious or spiritual.
Tumour factors
Patients with laryngeal recurrence or second primary
tumours have better outcomes. Patients with small loca-
lised tumours (low T stage (rT1–T2) and a low overall
stage8 and those with no neck disease on recurrence
demonstrate better outcomes. Patients with no nodal
extracapsular spread also have better outcomes.
Patients who have a recurrence more than 12 months
after the end of their treatment appear to do better.
Those with recurrence less than six months from treat-
ment completion have persistent disease and a much
worse prognosis.8 Finally, patients who have HPV
positive recurrent disease have longer survival follow-
ing treatment for recurrence.4
Treatment factors
Patients having surgical resection,2,4 who have received
no previous RT or chemotherapy8,9 or have not experi-
enced severe ongoing toxicity from previous treatment
appear to have the best outcomes, especially if they
have HPV-positive disease.4 Patients with resectable
disease with no gross tumour remaining after resection
and no involved surgical margins8 also demonstrate
better outcomes, as do patients with no involved vital
structures.
Surgery
General principles
From the data available, surgery appears to be the
modality that is likely to result in the best chance of
cure,2 especially if there is the possibility of receiving
adjuvant treatment post-operatively,8 or if the patient
has HPV-positive disease.4 The aim of surgical treat-
ment is to remove the whole tumour with wide clear
margins, leaving no gross residual tumour behind.
However, this will usually result in large defects requir-
ing reconstruction. The resulting large functional defi-
cits have to be balanced against the benefit of longer
survival and/or or improved palliation.
Surgical salvage is associated with high complica-
tion rates and morbidities. The Radiation Therapy
Oncology Group (RTOG) 91–11 study reported an
overall complication rate of 59 per cent, of which 19
per cent were classified as major complications.1 A
fistula rate of 30 per cent was reported following
salvage laryngectomy after chemoradiotherapy, and
15 per cent if they had been treated with RT. The
MD Anderson series of oropharyngeal salvage reported
an overall complication rate of 48 per cent.8 As a result
S184
of that and slower wound healing, patients experience
long stays in hospital, which they need to be fore-
warned about. Such treatment also carries significant
costs, which need to be accounted for in reimburse-
ment. Specific interventions that have been shown to
reduce complication rates are discussed below.
Recommendation
• Patients with recurrence should be assessed
systematically by a team experienced in the
range of management options available for
recurrence including surgical salvage,
re-irradiation, chemotherapy and palliative
care (R)
It is important to note that patients should undergo
appropriate and extensive counselling regarding
expected survival and functional outcomes, including
the long post-operative hospital stays and high compli-
cation rates. Early involvement of palliative care physi-
cians in the counselling and treatment of patients, even
in situations where curative treatments are being
offered, is of benefit to control symptoms and
provide psychological support.
Site-specific factors
Larynx. Total laryngectomy is a highly feasible and
effective treatment for laryngeal recurrence. In the
RTOG 91–11 study, 122 patients recurred after RT or
chemoradiotherapy, all of whom had salvage total lar-
yngectomy. The study reported two-year locoregional
control rates of 74 per cent and two-year overall sur-
vival of 71 per cent.1 However, it should be noted
that there are several other feasible and highly effective
modalities for the treatment of laryngeal recurrence that
may also allow preservation of organ function.
Transoral laser surgery has been found to be very
effective in well-selected patients. In a study of 34
recurrent T1–T4 post-RT failures, 71 per cent were
reported to be cured with one or more transoral laser
procedure, 29 per cent of patients had tumours that
could not be controlled, of which 18 per cent required
total laryngectomy and 9 per cent required palliative
treatment.10 In another study of 53 T1–T4 tumours that
recurred after RT,11 42 per cent were cured with one trans-
oral procedure and 16 per cent required more than one
procedure, 26 per cent could not be controlled and
required total laryngectomy and 11 per cent could not
undergo total laryngectomy for recurrence and required
palliative treatment. Transoral surgery should however
be performed in selected cases by experienced surgeons,
as a meta-analysis of transoral laser surgery for radiore-
current cancers showed around 30 per cent inferior
local control compared with open partial laryngectomy.12
A systematic review and meta-analysis of 554
patients who underwent salvage open partial laryngect-
omy concluded that the pooled locoregional control
H MEHANNA, A KONG, SK AHMED
rate was 87.2 per cent (83.3–90 per cent). Pooled
overall survival was 83.5 per cent (79.4–87.3 per
cent), with a pooled disease-free survival of 91.4 per
cent (88.0–94.2 per cent). While 97 per cent of patients
underwent successful decannulation, and of the 197
patients where swallowing outcomes were reported,
194 achieved full oral intake.13 Supracricoid laryngect-
omy alone was assessed in a meta-analysis of 103
recurrent T1 and T2 glottic cancer14 and local control
could be achieved in 85 per cent. In the 15 per cent
who had further recurrence, two thirds could be
treated further with salvage laryngectomy.
Therefore, total laryngectomy is not the only option
for treatment of laryngeal recurrence, and transoral and
partial laryngectomy operations are feasible and highly
effective. It is recommended that the management of
patients with laryngeal recurrence includes input from
surgeons who have expertise in transoral and open
partial laryngectomy in the recurrence setting, and
that this expertise is limited to a small number of sur-
geons providing regional services.
Recommendations
• Management of patients with laryngeal
recurrence should include input from
surgeons with experience in transoral surgery
and partial laryngectomy for recurrence (G)
• Expertise in transoral surgery and partial
laryngectomy for recurrence should be
concentrated to a few surgeons within the
MDT (G)
• Transoral or open partial laryngectomy
should be offered as definitive treatment
modality for appropriate highly-selected
patients with recurrent laryngeal cancer (R)
Oropharynx. Recent data suggest that the outcomes of
treatment of oropharyngeal recurrence have steadily
and markedly improved over the last two decades. In
a meta-analysis of five-year outcomes, survival out-
comes are reported to have increased from 18 per
cent for patients treated before the year 2000 to 51
per cent for patients treated after the year 2000.2 It
would also appear that the reported complication
rates have also decreased considerably over that
period of time. This improvement in outcomes may
be due to a combination of several factors: better
intra- and post-operative care, better use of reconstruct-
ive techniques, better patient selection and also the pos-
sible role of HPV. Recent data suggest that patients
with HPV-positive recurrence of the oropharynx have
longer survival rates than patients with HPV-negative
recurrence.4 Importantly, those patients who are HPV
positive and who received surgical resection had sig-
nificantly better outcomes than the other groups. This
would suggest that there is a need for a change in the
traditional view that patients with oropharyngeal
RECURRENT HEAD AND NECK CANCER: UK GUIDELINES
cancer have very poor outcomes, and therefore are
often offered palliative treatments instead of curative
resections. It should, however, also be noted that surgi-
cal treatment of recurrence carries significant complica-
tion rates as well as considerable functional deficits,
with reports on return to oral intake varying from 44
to 68 per cent.8 Successful resection of oropharyngeal
recurrence can be difficult due to the complex three-
dimensional anatomy and proximity and adherence to
the internal carotid artery. Access procedures through
mandibulotomy or lingual release are usually required.
Discussion with oncology colleagues regarding areas
of highest RT delivery can help plan the siting of the
mandibulotomy, as a median mandibulotomy may
avoid the areas of the mandible that received the
highest RT dose, and therefore avoid the areas at
highest risk of osteoradionecrosis. Lingual release is
also a good option, but provides limited access to the
superior aspects of lateral tonsillar extensions, and
may result in higher functional morbidity.
Recommendations
• Patients with oropharyngeal recurrence
should have p16 HPV status assessed (R)
• Patients with oropharyngeal recurrence
should be considered for salvage surgical
treatment by an experienced team, with
reconstructive expertise input (G)
• Transoral surgery appears to be an effective
alternative to open surgery for the
management of oropharyngeal recurrence in
carefully selected patients (R)
Recently the advent of transoral surgery, and especially
transoral robotic surgery (TORS), has facilitated better
transoral access to the oropharynx.15 This approach is
now being utilised for surgical resection of smaller
OPC recurrences with good outcomes. A recent multi-
centre case–control study showed that salvage patients
treated with transoral robotic surgery had significantly
lower incidence of tracheostomy, feeding tube use, and
shorter hospital stay, with significantly decreased inci-
dence of positive margins and significantly higher sur-
vival than matched patients treated with open surgery.
Nasopharynx. This is the one area traditionally where
re-irradiation has been employed for salvage treat-
ment, particularly where the recurrent disease is
limited to the confines of the nasopharynx without
extensive invasion of the bone of the skull base or
intracranial structures. In areas of the world where
major centres treat large numbers of these patients,
notably Southern China, Hong Kong and Singapore,
surgery for localised recurrent disease has been under-
taken by means of maxillary swing or other forms of
anterior mid-facial approaches. With varying degrees
of nasopharyngectomy, cure rates in selected patients
S185
have been reported in the region of 40 per cent at
five years.
Sinus and nasal cavity. Despite the rarity of these
tumours and the diversity of pathology in these areas,
salvage treatment can achieve good long-term cure
rates in carefully selected patients. Endoscopic endona-
sal surgery is showing comparable outcomes and is the
treatment of choice in certain situations for both
primary and recurrent disease when compared with
conventional open approaches.
Many recurrent tumours such as adenoid cystic car-
cinoma, chondrosarcoma, intestinal type adenocarcin-
oma and olfactory neuroblastoma will need a
multimodality, multidisciplinary approach, which can
only be effectively provided in large centres that have
the expertise both in endonasal and in open anterior
and anterolateral craniofacial resection. The tumour
biology as well as its location determines the best
approach. Oncological goals do not change in the endo-
scopic endonasal route with the goal being negative
resection margins. En-bloc resection is often not pos-
sible. Despite this, outcomes in both overall survival
and disease-free survival are comparable with open
approaches and should be considered as a viable treat-
ment option for recurrences.
Neck and nodal disease. Neck dissection in the salvage
context may carry higher complication rates than in the
primary setting. The type of neck dissection also has a
bearing on complication rates, with modified radical
neck dissections or radical neck dissections carrying
higher major complication rates than selective neck
dissections in the salvage setting. Furthermore, neck
dissection was found to be a significant risk factor
for pharyngocutaneous fistula after laryngectomy in a
meta-analysis.16 Studies looking at avoiding neck dis-
section in patients with recurrence at the primary site
with no clinical evidence of nodal metastasis have
shown that whilst the neck dissection is associated
with higher complication rates, there was also a
lower regional failure rate. On the other hand, other
studies have found the pre-operative clinical staging
of nodal status in patients undergoing salvage laryn-
gectomy to be highly accurate.17 Therefore it would
appear that undertaking elective neck dissections in
patients with N0 necks following recurrence should
be considered, especially in patients with advanced
recurrences.
As for patients with proven nodal recurrent disease,
selective neck dissection is also as effective as modified
radical neck dissections, but potentially carries less
morbidity.18 The evidence would suggest that using
selective neck dissection reduces complication rates
and results in similar control rates to more radical
neck dissection in recurrence patients who have N0.
Indeed, some have suggested that superselective neck
dissection is also effective, although the evidence
level for this is weak.19
S186
Recommendations
• Consider elective selective neck dissections in
patients with recurrent primaries with N0
necks, especially in advanced cases (R)
• Selective neck dissection (with preservation of
nodal levels, especially level V, that are not
involved by disease) in patients with nodal
(N+) recurrence appears to be as effective as
modified or radical neck dissections (R)
Reducing complications in salvage surgery
There are interventions that are proven to reduce compli-
cations in salvage surgery. These include the following:
• Use of Montgomery salivary bypass tubes has been
shown to decrease fistula rates and has also been
shown to be cost-effective in laryngectomy20
• The use of flap closure for pharyngeal defects if
there is any tension on wound closure has been
shown to decrease fistula rates. A meta-analysis
showed that use of a vascularised flap to augment
the circumference or support the repair reduces
the risk of fistula formation by one-third.13 Flap
reconstruction also reduces stricture rates and tube
dependence compared with primary closure. The
use of a pectoralis major pedicled-flap or a free
flap is therefore recommended
• In patients where there is no tension at the anasto-
motic site, interposition flap reinforcement of the
suture line has been shown to decrease fistula
rates. This may be undertaken using a pectoralis
major myofascial pedicled flap or an interposition
free flap, both of which have been shown to reduce
fistula rates13
• Secondary puncture has also been shown to
reduce fistula rates in post-chemoradiotherapy
salvage laryngectomies. Although no literature
evidence exists, avoidance of three-point junc-
tions in skin incision through the use of horizon-
tal incisions (e.g. Attee or MacFee) may help
reduce wound breakdown.
Palliative chemotherapy
Patients receiving only palliative care have an average
overall survival of four months after diagnosis.
Outcomes from studies of palliative chemotherapy
generally show longer survival rates, depending on
the regimen. However, no large well-designed rando-
mised trial has been undertaken to definitively show
an overall survival benefit of palliative chemotherapy
over the best supportive care in these patients.
Several chemotherapy regimens, either single agent
or combination treatments have been tried in recurrent
head and neck squamous cell carcinoma patients with
different results. The active single agents in head and
neck squamous cell carcinoma patients with response
H MEHANNA, A KONG, SK AHMED
rates greater than 15 per cent include methotrexate,
bleomyin, cisplatin, carboplatin, paclitaxel, docetaxel,
cyclophosphamide, doxorubicin, hydroxyurea, vinblast-
ine and fluorouracil (5-FU). Various randomised trials
have been undertaken to compare different chemo-
therapy regimens in recurrence patients. Combination
treatment has shown higher response rates than the
single-agent therapy.
In comparison with PF (cisplatin 100 mg/m2 and
5-FU 750 mg/m2 days 1–5 every three weeks) in a ran-
domised controlled trial, TPF induction chemotherapy
(docetaxel 75 mg/m2, cisplatin 75 mg/m2 and 5-FU
750 mg/m2 days 1–5 every three weeks) was shown
to yield a higher objective response rate as well as
increased median progression-free and overall survi-
vals in unresectable head and neck cancer patients
without distant metastasis. However, this regimen is
mainly used as induction chemotherapy before radical
treatment for curative patients and it is not normally
used as first line treatment in recurrent or metastatic
head and neck squamous cell carcinoma patients with
unresectable disease due to significant toxicities asso-
ciated with this regimen.21 Some of the selected
chemotherapy regimens commonly used in palliative
head and neck squamous cell carcinoma patients are
listed in Table I.
Recommendations
• Use salivary bypass tubes following salvage
laryngectomy (R)
• Use interposition muscle-only pectoralis
major or free flap for suture line
reinforcement if performing primary closure
following salvage laryngectomy (R)
• Use inlaid pedicled or free flap to close wound
if there is tension at the anastomosis following
laryngectomy (R)
• Perform secondary puncture in post CRT
laryngectomy patients (R)
Since a majority of head and neck squamous cell carcin-
oma tumours express or overexpress epidermal growth
factor receptor, the epidermal growth factor receptor
inhibitors including cetuximab has been tried in these
patients. A phase III randomised trial of cisplatin plus
placebo compared with cisplatin plus cetuximab in meta-
static and/or recurrent head and neck cancer was done
and it was shown that addition of cetuximab to cisplatin
significantly improved response rate but did not signifi-
cantly improve progression-free and overall survival.22
The addition of cetuximab to platinum-based chemo-
therapy (either cisplatin 100 mg/m2 or carboplatin are
under the curve 5 with 5-FU 750 mg/m2 days 1–4
every three weeks) improved objective response rate,
median progression-free and overall survivals compared
to platinum-base chemotherapy alone (EXTREME
RECURRENT HEAD AND NECK CANCER: UK GUIDELINES S187

TABLE I
SELECTED PALLIATIVE CHEMOTHERAPY REGIMENS COMMONLY USED IN RECURRENT OR METASTATIC HEAD AND
NECK SQUAMOUS CELL CARCINOMA PATIENTS (MODIFIED FROM REFERENCES 1–2)
Regimens Usual doses Response Reference
rate (%)

Cetuximab/5-FU/cisplatin Cisplatin IV 100 mg/m2 q3w 36 Gao et al.6

5FU IV 1000 mg/m2 d1–4 q3w
cetuximab IV 400 mg/m2 loading dose
and 250 mg/m2 maintenance dose q1w
Cisplatin/5-FU Cisplatin IV 100 mg/m2 q3w 27–50 Jayaram et al.2, Zafereo et al.8,
5FU IV 1000 mg/m2 d1–4 q3w Paleri and Kelly9
Cisplatin/paclitaxel Cisplatin IV 75 mg/m2 q3w 26–41 Zafereo et al.8, Steiner et al.10
paclitaxel IV 175 mg/m2 q3w
Cisplatin/docetaxel Cisplatin IV 75 mg/m2 q3w 53 Roedel et al.11, Ramakrishnan
docetaxel IV 75 mg/m2 q3w et al.12
Carboplatin/paclitaxel Carboplatin IV AUC 6 q3w with 27 Paleri et al.13, Marioni et al.14
paclitaxel IV 200 mg/ m2 q3w or 52
carboplatin IV AUC 2 q1w with
paclitaxel 80 mg/m2 q1w
Docetaxel Docetaxel 75–100 mg/m2 q3w 21–42 White et al.15, Paydarfar et al.16
Paclitaxel Paclitaxel 80–100 mg/m2 q1w 13–40 Pezier et al.17, van der Putten
paclitaxel 175 mg/m2 q3w et al.18
Methotrexate Methotrexate 40–60 mg/m2, q1w 10–77 Dunsky et al.7, Robbins et al.19,
Murray et al.20
IV = intravenous; q3w = every three weeks; q1w = every week; d1–4 = days 1–4
Note: some of the trials used different doses and regimens than those listed as ‘usual’ doses.

trial).23 This regimen is recommended as the first-line
systemic treatment for recurrent and metastatic head
and neck squamous cell carcinoma patients with good
performance status in many centres. However, the
choice of EXTREME regimen as first-line treatment
will depend on individual patient circumstances and per-
formance status. In England, cetuximab in addition to 5-
FU and platinum chemotherapy could be prescribed in
the NHS through the cancer drug fund although this
fund is not available in other parts of the UK and may
only be available in the a short term. As the regimen is
associated with high frequencies of toxicities, not all
patients can tolerate or complete the treatment.
For patients who are deemed to be unfit to have
EXTREME regimen, a modified version of cetuximab
and a platin or reduced doses have been used for some
patients. In addition, if cetuximab is not used or not
available, many centres will use the combination plat-
inum-based regimens (without cetuximab) as first-line
treatment for these recurrent head and neck squamous
cell carcinoma patients, including those regimens
listed in Table I.
Once patients have progressed on platinum based
chemotherapy, the prognosis is extremely poor and
there is no standard second-line or third-line therapy
for these patients. In some cases, another platinum-
based combination chemotherapy can be given as
second line, e.g. carboplatin and paclitaxel. However,
some of these patients may have deteriorating or poor
performance status and further combination chemo-
therapy treatment may be poorly tolerated. In addition,
some patients may be platinum-resistant and are unlike-
ly to benefit from further platinum-based chemother-
apy. For second- or third-line chemotherapy, single
agent taxane (paclitaxel or docetaxel) or methotrexate
has also been used in patients who still have relatively
good performance status.
For patients who are unfit to have palliative chemo-
therapy, best supportive care may be the best option,
since palliative chemotherapy may worsen their
quality of life without a survival benefit. This decision
needs to be made by the doctors and patients together,
with the involvement of a palliative care physician,
focusing on the benefits of palliative chemotherapy
vs the risks of treatment toxicity.
Patients with non-resectable recurrences being con-
sidered for palliative treatment should be offered the
opportunity to participate in clinical trials of new thera-
peutic agents, including immunotherapy. If such trials
are not available locally, patients should be referred
to centres that offer these trials.
Recommendations
• Triple therapy with platinum, cetuximab and
5-fluorouracil appears to provide the best
outcomes for the management of patients with
recurrence who have a good performance
status and are fit to receive it. If not fit, then
combinations of platinum and cetuximab or
platinum and 5-FU may be considered (R)
• Patients with non-resectable recurrent disease
should be offered the opportunity to
participate in Phase I-III clinical trials of new
therapeutic agents (R)
Re-irradiation
Most patients with recurrence will have had previous
radical RT, which would have reached the maximal
S188
acceptable tolerance dose for critical organs such as
spinal cords and/or brainstem. Therefore, re-irradiation
of these patients carries significant potential risks and
complications.
Patient selection
Data on patient selection for chemo re-irradiation is
sparse, with comorbidity and pre-existing organ dys-
function being the most important prognostic factors
for patients undergoing re-irradiation. Other prognostic
factors include interval from previous radiation, recur-
rent tumour stage, tumour bulk at re-irradiation, and re-
irradiation dose.24
Re-irradiation using conventional and older RT
techniques for unresectable recurrent cancers
Some single centre and phase 2 studies have shown
very good control rates for re-irradiation of recurrent
tumours with prolonged survival rates. However, repli-
cation of these results in phase 3 studies has not mate-
rialised, probably reflecting in part the importance of
specialist expertise and careful patient selection. At
the Gustave-Roussy Institute, full-dose re-irradiation
was given to 169 patients with unresectable head and
neck cancer, in the form of either RT alone or with con-
current chemotherapy (5-FU and hydroxyurea or mito-
mycin, 5-FU and cisplatin). The overall survival (OS)
rate was 21 per cent at 2 years and 9 per cent at 5
years, with a median survival time of 10 months for
the whole population. In the RTOG 96–10 study, 86
patients received re-irradiation with 5-FU and hydro-
xyurea. The two- and five-year survival rates were
15.2 and 3.8 per cent respectively with overall grade
3–4 acute toxicities of 56 per cent, grade 3–4 late toxi-
cities of 22 per cent and deaths in 8 per cent of
patients.25 In the RTOG 99–11 study, recurrent head
and neck cancer patients received twice-daily radiation
(1.5 Gy per fraction bid 5 days every 2 weeks with low-
dose paclitaxel and cisplatin). The estimated one- and
two-year OS rates were 50.2 and 25.9 per cent, respect-
ively. The study also showed 28 per cent grade 4–5
acute toxicities and 11 per cent treatment-related
deaths.
A randomised phase III trial (Groupe d’Oncologie
Radiotherapie Tete Et Cou (GORTEC) 98–03) com-
pared re-irradiation with 5-FU and hydroxyurea
chemotherapy with palliative methotrexate monother-
apy in patients with recurrent or a second primary
head and neck squamous cell carcinoma.26 Despite
the promising phase II studies, this phase III study
showed that re-irradiation with concurrent chemother-
apy did not improve OS compared with methotrexate
alone (23 per cent vs 22 per cent at one year, NS).
There were however four complete responses in the
re-irradiation arm, and none in the chemotherapy
alone arm. Twenty-eight per cent had grade 3 late tox-
icity in the re-irradiation arm compared with 9 per
cent in the chemotherapy arm. The trial was closed
H MEHANNA, A KONG, SK AHMED
prematurely and thus no definite conclusion could
be drawn.
The Groupe d’Étude des Tumeurs de la Tête et du
Cou (GETTEC) and Groupe d’Oncologie Radiothera-
pie Tête Et Cou (GORTEC) undertook a randomised
study examining the efficacy of adjuvant chemo re-
irradiation after salvage surgery. The study included
patients who had salvage surgery with no gross residual
disease and a good performance status. Patients were
randomised to either observation or post-operative
chemo re-irradiation (FHX (5-fluoro-uracil, hydroxyurea
and radiation) regimen, daily radiation to 60 Gy).
Patients in the post-operative chemo re-irradiation arm
had significantly improved locoregional control (49
per cent vs 25 per cent) and disease-free survival.
However, there was no significant difference in overall
survival due to an increase in treatment-related deaths
and second primary tumours following chemo re-irradi-
ation, with 40 per cent of patients experiencing grade 3
or 4 late toxicity in the chemo re-irradiation arm, com-
pared to 10 per cent in the observation arm.
Re-irradiation with intensity-modulated radiotherapy
(IMRT)
Intensity-modulated radiotherapy (IMRT) can poten-
tially limit the dose to critical areas. At the same
time, however, it may increase the dose to surrounding
non-critical areas. Therefore, it is not yet completely
clear what the balance of benefit and harm will be.
In one study, 105 patients with recurrent head and
neck cancer underwent re-irradiation using IMRT
(75 of whom also received concurrent chemotherapy)
and the two-year locoregional progression-free sur-
vival and overall survival rates were 42 and 37 per
cent, respectively. The acute and late grade 3 toxicities
were reported in 23 and 15 per cent of patients respect-
ively. In another study, 84 patients underwent re-irradi-
ation using IMRT (20 per cent received concurrent
chemotherapy), five-year locoregional control and
overall survival were 40 and 20 per cent respectively,
with grade 3 acute and late toxicities of 31 and 13 per
cent. Although there was no grade 5 acute toxicity,
there were two fatal vascular ruptures during follow-up.
Re-irradiation with biological therapies
The combination of an epidermal growth factor recep-
tor inhibitor, cetuximab, with RT has been shown to
significantly improve overall survival at five years
compared with RT alone for locoregionally advanced
head and neck cancer. Therefore, there is also rationale
for combining cetuximab with re-irradiation in recur-
rent head and neck cancer patients. One recent study
showed a median overall survival of 10 months in
recurrent head and neck cancer patients retreated with
stereotactic body radiation therapy plus cetuximab.
Acute and late grade 3 toxicity was observed in 6 per
cent of patients, which seems to be much lower than
that of re-irradiation and chemotherapy.
RECURRENT HEAD AND NECK CANCER: UK GUIDELINES
Toxicity of chemo re-irradiation
Chemo re-irradiation carries risk of very severe life-
threatening toxicity, which has to be weighed against
the relative survival benefit, and quality of life detri-
ment. The resultant acute major toxicities are similar
to those of primary chemoradiotherapy, including
mucositis, dermatitis and hematologic suppression.
These toxicities generally resolve after the completion
of therapy, and most patients recover with supportive
measures, although treatment interruptions may be
necessary. Compared with re-irradiation alone, the add-
ition of concurrent chemotherapy significantly
increases acute toxicities.
Late toxicities are generally less predictable and irre-
versible, and therefore carry a higher potential for pro-
blems. In RTOG 9610, the cumulative incidence of
grade 3+ late toxicity in patients surviving more than
1 year was 12.3 per cent. The most worrisome late com-
plications are neurological toxicities as well as carotid
rupture. Fortunately, these devastating complications
occur rarely, even in patients who receive large lifetime
radiation doses.
Recommendations
• Chemo re-irradiation appears to improve loco
regional control, and may have some benefit
for overall survival, at the risk of considerable
acute and late toxicity. Benefit must be
weighed carefully against risks, and patients
must be counselled appropriately (R)
• Target volumes should be kept tight and
elective nodal irradiation should be avoided
(R)
Treatment volume definition
In re-irradiation, the potential benefit and toxicity of
elective nodal irradiation need to be carefully consid-
ered, since the risk of toxicity is generally related to
the volume of tissue irradiated. The literature suggests
that the major risk of recurrence is within the region of
gross recurrent disease. The probability of isolated
failure in the electively treated areas is low. Treatment
volume of the gross tumour should be expanded by a
safety margin of 1–1.5 cm. Prophylactic treatment of
draining lymphatic regions is generally avoided. In
areas closely abutting critical structures, the margin
may be smaller to reduce the risk of complications.
After surgical resection, only the tumour bed of the
high-risk areas (e.g. positive margin and extracapsular
extension) is usually targeted.
Best supportive care
Palliative and best supportive care should be offered
routinely as part of the management package of all
recurrence patients, even in the case of those who are
being treated curatively. The early involvement of the
S189
palliative care physician can help control symptoms
in the lead up to curative or palliative treatment.
Furthermore, it provides a more seamless transition
into palliative care if required. Involvement of a pallia-
tive care physician gives the patients confidence that
their symptoms will be managed regardless of the out-
comes of the treatment, and also can speed up the pro-
vision of support for patient and family at home.
Key points
• Recent evidence suggests that outcomes of the
management of recurrence are not as dire as is
widely considered
• Evaluation and careful selection of patients with
recurrence is the crux of successful management
• PET CT scanning is the most effective imaging
method for the evaluation of recurrence
• Surgery appears to give the best outcomes for the
management of recurrence, especially if HPV
positive, but also has a high complication rate
• Patients who have the best outcomes from treat-
ment are those with small recurrences and
second primaries who do not smoke or who
have stopped smoking, and have good perform-
ance status, and in whom the tumour can be com-
pletely removed with no involved margins,
especially if chemoradiotherapy can be given
afterwards if indicated
• The standard regimen for first-line palliative chemo-
therapy is cisplatin, 5-FU and cetuximab. However
some patients may not be able to tolerate it
• Re-irradiation using tight target volumes may
improve locoregional control, but does carry sig-
nificant risk of toxicity
• Patients with recurrence often have significant
symptoms, and should be offered best supportive
care interventions regardless of the intent of
therapy, as they can benefit from assessment and
management by pain control teams and other
clinicians.
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11 Roedel RM, Matthias C, Wolff HA, Christiansen H. Repeated
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H, Jones T et al. Oncologic outcomes of transoral laser micro-
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13 Paleri V, Drinnan M, van den Brekel MW, Hinni MW, Bradley
ML, Wolf PJ et al. Vascularized tissue to reduce fistula
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of supracricoid laryngectomy for glottic carcinoma recurrence
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2006;126:1245–51
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surgery: a meta-analysis of postlaryngectomy pharyngocutaneous
fistula. Arch Otolaryngol Head Neck Surg 2006;132:67–72
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MWM, Balm AJM, Hoebers FJP et al. Effectiveness of salvage
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S, Clark JR et al. Functional outcomes and donor site morbidity
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Degardin M et al. Cisplatin, fluorouracil, and docetaxel in unre-
sectable head and neck cancer. N Engl J Med 2007;357:
1695–704
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8646–54
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Rottey S et al. Platinum-based chemotherapy plus cetuximab
in head and neck cancer. N Engl J Med 2008;359:1116–27
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DeConti R et al. Prognostic factors for survival after salvage
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1983–91
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Spanos W et al. Final report of RTOG 9610, a multi-institutional
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Bardet E et al. Randomized phase III trial (GORTEC 98–03)
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Address for correspondence:
Prof Hisham Mehanna,
Institute of Head and Neck Studies and Education,
College of Medical and Dental Sciences, University of Birmingham,
Edgbaston, Birmingham, UK
E-mail: h.mehanna@bham.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S191–S197. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000621

Reconstructive considerations in head and neck

surgical oncology: United Kingdom National
Multidisciplinary Guidelines

M RAGBIR1, J S BROWN2, H MEHANNA3

1
Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, 2Department of Oral and
Maxillofacial Surgery, Aintree University Hospitals NHS Foundation Trust, Liverpool University, Liverpool, and
3
School of Cancer Sciences, Institute of Head and Neck Studies and Education, University of Birmingham,
University Hospital Birmingham, Heart of England NHS Foundation Trust, Birmingham, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. The reconstructive needs following ablative surgery for head and neck cancer are unique and
require close attention to both form and function. The vast experience accrued with microvascular reconstructive
surgery has meant a significant expansion in the options available. This paper discusses the options for
reconstruction available following ablative surgery for head and neck cancer and offers recommendations for
reconstruction in the various settings.

Recommendations
• Microsurgical free flap reconstruction should be the primary reconstructive option for most defects of the head
and neck that need tissue transfer. (R)
• Free flaps should be offered as first choice of reconstruction for all patients needing circumferential
pharyngoesophageal reconstruction. (R)
• Free flap reconstruction should be offered for patients with class III or higher defects of the maxilla. (R)
• Composite free tissue transfer should be offered as first choice to all patients needing mandibular
reconstruction. (R)
• Patients undergoing salvage total laryngectomy should be offered vascularised flap reconstruction to reduce
pharyngocutaneous fistula rates. (R)

Introduction stage reconstruction utilising vascularised tissues with

The problems of reconstructive surgery for the head
and neck are variable and can be very complex.1,2
These guidelines have been divided into the manage-
ment of the loss of skin, the maxilla, the mandible,
including the associated soft tissues, the oropharynx
and the laryngopharynx. There is very little level 1 evi-
dence relating to the reconstruction of head and neck
defects. Mandibular reconstruction techniques are
fairly standard but some controversy remains regarding
the midface and maxilla because of the complexity of
the defects and the possibility of using a dental or
facial prosthesis.
Most reconstructions are performed primarily follow-
ing tumour extirpation, but secondary reconstructions
are also undertaken to treat problems such as fistulae
or osteoradionecrosis. Modern techniques aim for one
a high success rate and good overall results.
Priorities of reconstruction include restoring oral
cavity lining, maintaining oral competence, maintain-
ing function of speech and swallowing and providing
an acceptable aesthetic result. Choice of reconstructive
options depends on patient comorbidities, factors
relating to the surgical defect, any future possible treat-
ments including radiotherapy and donor site morbidity.
No appropriately powered randomised controlled trials
exist to determine flap selection in most instances and
this is usually determined by the expertise of the
individual surgeon. Patient factors include prior treat-
ments, especially surgery and radiotherapy and the
patient’s overall health including medical and social
history. Multiple tissue types often require to be
reconstructed.
S192
Oral cavity soft tissues
Oral soft tissues include tongue, floor of mouth, buccal
mucosa and the retro-molar trigone extending to the
tonsillar area. It is rare that only one of these areas is
involved. Reconstructive access is usually determined
by the extent of surgical resection and may involve a
lip-split and mandibular osteotomy, although a per-
oral approach is usually possible.
Microsurgical techniques provide the mainstay of
oral soft tissue reconstructions as they allow import-
ation of large volumes of healthy tissue from sites
distant to prior surgical or radiotherapy fields. Flaps
commonly used include the radial forearm flap (RFF)
and the anterolateral thigh (ALT) flap. Less commonly
the latissimus dorsi, rectus abdominus and flaps based
on the scapular and/or para-scapular axis are utilised.
More recently, the medial sural artery perforator flap
(MSAP) and the superficial circumflex iliac artery per-
forator flap are being used. The first two represent the
workhorse flaps in this field and will be discussed
separately.
The RFF allows for importation of a large, thin,
pliable flap with excellent reliability and simplicity of
harvest.3 Multiple skin paddles can be designed and
the flap can be raised as a cutaneous, fasciocutaneous,
fascial, adipofascial, osseo-fascial or osseo-cutaneous
flap (see below). The principal disadvantage of this
flap is the poor donor site aesthetics when skin grafting
is required.
The ALT flap allows for importation of very large
tissue volumes and is versatile.4 Fascio-cutaneous and
fascial flaps can be raised, along with muscle and
fascia lata if required. The flap has a long pedicle,
but can be technically challenging to raise. It is a rela-
tively thick flap which can be thinned. If multiple per-
forating vessels are available, then the flap can be
raised with two skin paddles. Donor site morbidity is
minimal and use of the ALT is increasing in most
reconstructive centres.
If microsurgery is considered, inadvisable local or
regional flaps are still used. Within the oral cavity
local mucosal flaps can be useful to help close small
defects. Regional flaps such as pectoralis major and
deltopectoral can be effective in importing tissue, but
are not generally considered as a first choice.
Mandible
Reconstruction of the mandible must address the site
and size of the bony defect, associated soft tissue loss
and the desirability of dental rehabilitation. Free
tissue transfer is the mainstay of mandibular recon-
struction as it allows importation of bone which can
be tailored to fit the desired shape, is well vascularised
and is amenable to osseo-integration. Several flaps are
commonly used with high success rates, including the
fibula flap, deep circumflex iliac artery (DCIA) flap,
scapular flap and RFF.5
M RAGBIR, J S BROWN, H MEHANNA
The fibular flap allows harvest of a long piece of bone
which is of adequate height for osseo-integration and
can be osteotomised several times for contouring.6,7
This is now made easier with the availability of software
to plan the osteotomies at the mandible and on the fibula
prior to transfer. It is relatively easy to harvest as an
osseus or osteoseptocutaneous flap, with or without
muscle. This versatility means it is the workhorse for
mandibular reconstruction in most centres. One draw-
back of the flap is its relative lack of height.
The DCIA flap provides for a high bony segment
and the natural curve of the ilium lends itself to
lateral mandibular defects where an osteotomy may
not be necessary. The donor site defect can be problem-
atic and its skin paddle is usually reserved for external
use although muscle can be incorporated for oral
reconstruction.
The scapular flap allows for harvest of a relatively
small amount of bone. The main advantage of this
flap is the large volume of skin and muscle (latissimus
dorsi) which can be used. The bone is a good height,
but two-team flap harvesting is generally not possible.
Radial forearm flap is rarely used for bone recon-
struction as only a small volume of bone of low
height can be harvested. There is a risk of subsequent
fracture of the radius.
A new classification of the mandibular defect has
been described based on the four corners of the mandible
which are both angles and both canines (Figure 1):8
• Class I (70 mm)/Ic (84 mm): Subcondylar region
to the ipsilateral canine and class Ic includes the
condyle. Most of the flaps described above will
work well as the length of this defect is around
7–8 cms and so all bone donor sites are adequate.
In the lateral defect the height of the reconstruction
is less problematic.
• Class II (85 mm)/IIc (126 mm): Hemimandibu-
lectomy from subcondylar region including ipsi-
lateral canine and class IIc includes condyle. The
iliac crest can work well as the shape of the ipsilat-
eral hip may reduce osteotomy preparation and a
scapula may not be sufficiently long for a class
IIc when soft tissue is seldom an issue.
• Class III (100 mm): Includes both canines, but
neither angle. The choice of flap depends more
on the plan of rehabilitation and height of chin
support. The fibula flap can be double-barrelled
to increase height, but scapula and radius are
often difficult to implant successfully for complete
oral rehabilitation.
• Class IV (152 mm)/IVc (168 mm): This is an
extensive mandibulectomy including at least one
angle and both canines. The fibula flap is
usually the best option for faithful reconstruction,
but the mandible is often best made smaller for
such major resections especially if there is loss
of maxillary teeth.
RECONSTRUCTIVE CONSIDERATIONS IN HEAD AND NECK SURGICAL ONCOLOGY: UK GUIDELINES S193

FIG. 1
Classification of mandibular defects.

Dental rehabilitation is a key part of mandibular defects of an orbitomaxillary (class V) or nasomaxil-

reconstruction and pre-operative liaison with an appro-
priate team including consideration of osseo-integrated
implants is mandatory.
Maxilla and midface
The level of evidence is very weak in all areas of recon-
struction, but more particularly in the maxilla and
midface because of the differing complexity of the
defects, and the potential for skull base involvement.
Throughout this section, it is necessary to refer to the
classification suggested in Fig. 2.9 The choice of a
prosthetic option or reconstruction depends on the
nature of the defect. In class I and II defects an obtur-
ator is a reasonable option, but this becomes less
favourable as the orbital adnexae are involved (class
III), orbital exenteration (class IV) and the midface
lary (class VI) nature. This refers not only to the verti-
cal component but also to the extent of the dental or
alveolar part of the resection relevant to the prostho-
dontist in deciding on appropriate obturation. Other
classifications suggested include those by Okay et al.,
but there is no distinction between classes III and IV.
All cases involving the loss or ablation of the maxilla
and/or midface should be discussed in a multidiscip-
linary setting. The choice of reconstruction or prosthe-
tics requires discussion among the ablative and
reconstructive teams, the prosthodontist, maxillofacial
technician, the patient and the family. There are clear
advantages in simplifying the surgery and using pros-
thetic options, but this choice becomes more difficult
to deliver and for the patient to cope as the defect
becomes larger and more complex.
S194
FIG. 2
Classification of the maxillary and midface defects. Classes I–VI relate to the vertical component of the defect including orbitomaxillary (class
V) and nasomaxillary (class VI) when often the palate and dental alveolus are intact. Classes a–d relate to the increasing size of the palatal and
dento-alveolar part of the defect indicating increasing difficulty in obtaining good results with obturation.
Class I: This includes resections of the alveolar bone
not resulting in an oroantral fistula and these can either
be left to granulate or treated with a local flap. Also
included are defects involving the junction of the
hard and soft palate usually obturated or reconstructed
with a soft tissue flap, and minor maxillectomies which
may occur following the removal of small inverted pap-
illomas which generally do not require rehabilitation.
Class II: This is the standard hemimaxillectomy not
involving the orbital floor or adnexae. Obturation is
often very successful for this form of defect as the orbit
does not require support and if the defect is not too
large there is less of a problem for the patient in terms
of retention and stability of the prosthesis. In more exten-
sive cases (classes IIc–d), it is possible to gain very good
retention with an implant-retained prosthesis, although
reconstruction with the fibula flap has also shown good
outcomes. A vascularised bone with greater height,
such as the DCIA flap which includes the iliac crest and
internal oblique muscle, will give better support to the
peri-nasal area. The scapula flap can be supplied by the
circumflex scapular artery which supplies the lateral
scapula (scapula flap) through peri-osteal perforators
along its length or the angular branch of the thoracodorsal
artery which supplies the scapula tip. The advantage of
the scapula tip option is that the pedicle is considerably
longer than the circumflex scapula artery option which
is a great advantage in the maxilla and midface as the
recipient vessels are more distant.
Class III: In these cases, there is loss of the orbital
support and often a part of the nasal bones may also
require reconstruction. There is good consensus in the lit-
erature that the restoration of orbital support with vascu-
larised tissue (pedicled or free flap) is essential to
ensure healing of the bone graft and reduce the soft
tissue problems such as epiphora and ectropion. The
iliac crest with internal oblique provides the best solution
M RAGBIR, J S BROWN, H MEHANNA
if an implant-retained prosthesis is planned, but the
scapula tip flap using latissimus dorsi muscle is also a
good option with a more reliable pedicle. The fibula is
also described for this defect but considerable skill in
the adaptation of this flap for the defect is required with
variable results. The rectus abdominus with non-vascu-
larised bone is also an option but is associated with a
high ectropion rate and there is a risk of bone loss if radio-
therapy is required. The vastus lateralis based on the des-
cending branch of the lateral circumflex femoral artery is
another option.
Obturation alone will result in facial collapse, poor
support of the orbit and a high risk of vertical orbital
dystopia and ectropion. In children, the scapula tip
will probably be the best option as the iliac crest has
a cartilaginous cover and the vessels are much smaller.
Class IV: Reasonable results can be achieved with a
soft tissue flap alone such as rectus abdominus or
vastus lateralis but this will result in poor definition
of the orbital defect and some facial collapse. The
choice is similar to class III in that the iliac crest with
internal oblique offers better implant options but the
scapula tip flap is also a good option.
Class V: In the orbitomaxillary defect, the main aim
is not to obturate the orbital space with too much soft
tissue so as to allow space for an orbital prosthesis.
The temporalis or temporoparietal flap are ideal, but
in more extensive defects it is worth considering the
radial or ALT in a thinner patient.
Class VI: If there is loss of the facial skin between the
orbits and nasal bones, then free tissue transfer is prob-
ably essential. The composite RFF can be ideal if har-
vested with fascia to line the nasal side of the radial
strut and the skin to restore the face. The composite
radial can be augmented with a glabella or forehead
flap. A classical rhinectomy can be rehabilitated with a
prosthesis and of course the surgeon can check the
RECONSTRUCTIVE CONSIDERATIONS IN HEAD AND NECK SURGICAL ONCOLOGY: UK GUIDELINES
margins of resection and resect more tissue if required.
There are very successful full rhinectomy reconstructions
performed which can give a permanent biological solution
if preferred. In this defect attention must be paid to the res-
toration of the nasal bones with vascularised tissue to
prevent complications during and following radiotherapy.
Oropharyngeal reconstruction
The oropharynx can be divided into the walls of the
oropharynx (lateral and posterior), the base of the
tongue and the soft palate. The oropharynx is a muscu-
lar tube connecting the larynx and hypopharynx to the
oral cavity. The role of reconstruction is to try and
maintain the function of the residual tissue. From a
functional point of view the most difficult area is the
posterior tongue which allows normal movement of
the epiglottis and maintains swallowing and speech.
The use of transoral robotic and laser resections
without reconstruction may give better functional
results than reconstructing this muscular tube with
non-sensate skin such as the radial forearm flap.
Reconstruction of the soft palate
The most commonly described method of soft palate
reconstruction involves the use of the RFF often in
combination with a local flap such as the superiorly
based pharyngeal flap or the superior constrictor
advancement flap. Some suggest the use of a folded
RFF which is de-epithelialised in order to be sutured
to the de-epithelialised posterior pharyngeal wall, but
a superiorly based pharyngeal flap can be utllised to
provide the nasal lining with good results.10,11 The
free flap is used in the horizontal part of the defect
only if it is possible to close the posterior tongue to
narrow the pharynx and maintain its function.
Reconstruction of the pharyngeal walls and
tonsillar regions
Placing free tissue transfers will disrupt the muscular
tube and probably decrease function. For this reason,
transoral robotic and laser resections are preferred to
address these tumours where possible.
Reconstruction of the posterior tongue
Most surgeons do not claim to be able to restore func-
tion in this region if more than half of the posterior
tongue requires resection (Table I).
Pharyngo-laryngectomy reconstruction
Partial pharyngeal defects
Partial pharyngeal defects with more than 3.5 cm of
remaining pharyngeal mucosal width may be closed
primarily. Defects with less than 3.5 cm of pharyngeal
mucosal width remaining may be reconstructed using a
pedicled flap – usually a pectoralis major myocuta-
neous flap. Free flaps, such as radial forearm free
flaps, may also be used. If the pharyngeal mucosal
remnant is very narrow (<1 cm in width), then it is
S195
TABLE I
METHODS OF SOFT PALATE RECONSTRUCTION
No Obturation
reconstruction
Local flaps Superiorly based pharyngeal
Palatoplasty and lateral pharyngeal
Palatal island mucoperiosteal
Palatal island and pharyngeal
Masseter and buccal mucosa transposition
Masseter, buccal mucosa and pharyngeal
Temporalis
Superior constrictor advancement
Velopharyngoplasty or masseter and buccal
advancement
Pedicled flaps Temporal osteocutaneous island
Galeo-peri-cranial
Free flaps Radial forearm
Radial forearm and additional local
Folded radial forearm
Lateral arm
Jejunum
Anterolateral thigh
often better to excise the remnant and undertake a
total circumferential reconstruction.
Total circumferential pharyngolaryngectomy defects
Lower anastamosis above clavicles. Where the lower
anastamosis of a total circumferential pharyngolaryn-
gectomy reconstruction would lie above the clavicle,
several options exist:12 jejunal free flap (JFF), gastro-
omental free flap (GFF), tubed radial forearm free
flap (RFFF) and tubed anterolateral thigh free flap
(ALTF). All of the above options carry the risk of
free flap failure, anastamotic leaks, anastamotic stric-
tures, donor site morbidity, failure of voice rehabilita-
tion, swallowing problems and a small peri-operative
mortality rate.
Previously untreated cases. In previously untreated
cases, ALTs, tubed over a salivary bypass tube,
appear to provide the lowest complication rates –
with minimal donor site morbidity, lower leak rates
and lower stenosis rates. Good swallowing and voice
rehabilitation have also been reported. Alternatives
include the JFF13 and the RFF. Swallowing problems
due to hyper-peristalsis and a ‘wet’ sounding voice
are common with JFF, which also carries a morbidity
rate due to abdominal complications (≈5 per cent).
Radial forearm flap carries lower donor morbidity
rates, but higher stenosis and leak rates than JFF.
Tubing of the RFF over a salivary bypass tube
appears to decrease fistula rates.14
Post-chemoradiotherapy (salvage) cases. In general,
reconstructive free flap surgery in the salvage setting
carries higher risks of complications due to the deleteri-
ous effects of chemoradiotherapy on tissue vascularity
and wound healing. In such cases, limited case series
suggest that use of GFFs may have an advantage due
to the availability of the omentum. This can be
S196
wrapped around the anastamotic site to decrease the pos-
sibility of leakage and also improve the overlying skin
quality. Additional vascularised tissue can be included
with the ALT as a chimaeric flap to resurface the neck
in cases where there is poor quality skin or contracted
skin that would not safely close post-operatively.
Any of the other options mentioned previously, for
example JFF, RFF, may also be used in salvage surgery.
Lower anastamosis below clavicles. If the resection
extends to below the level of the clavicles, then a
gastric pull through or colonic transposition flap may
be used. Both these techniques carry significant mor-
bidity and mortality due to the need to enter three vis-
ceral cavities. Gastric pull through carries a mortality
rate of 5–15 per cent, morbidity of 30–55 per cent
and reported fistula rates of 3–23 per cent. Colonic
transposition carries similar risks, and appears to be
less commonly used. It can however provide a higher
reach than gastric pull through, and is therefore useful
for tumours that extend up high into the oropharynx.
Vascularised tissue after salvage
laryngectomy
Pharyngocutaneous fistulae (PCF) are known to
occur in nearly one-third of patients who undergo
salvage total laryngectomy after chemoradiation.
Pharyngocutaneous fistulae have severe impact on dur-
ation of admission and costs, quality of life and can
even cause severe complications such as bleeding,
infection and death. Recent meta-analyses suggest
that there is a clear advantage in using vascularised
tissue from outside the radiation field in the laryngect-
omy defect, either as a buttress or to augment the cir-
cumference of the pharynx.15,16 This intervention
reduces the risk of PCF by one-third to a half.
Recommendations
• Microsurgical free flap reconstruction should
be the primary reconstructive option for most
defects of the head and neck that need tissue
transfer (R)
• Free flaps should be offered as first choice of
reconstruction for all patients needing
circumferential pharyngoesophageal
reconstruction (R)
• Free flap reconstruction should be offered for
patients with class III or higher defects of the
maxilla (R)
• Composite free tissue transfer should be
offered as first choice to all patients needing
mandibular reconstruction (R)
• Patients undergoing salvage total laryngectomy
should be offered vascularised flap
reconstruction to reduce pharyngocutaneous
fistula rates (R)
M RAGBIR, J S BROWN, H MEHANNA
Key points
Mandible and oral cavity
• The radial forearm and the anterolateral thigh free
flaps are the preferred options for oral soft tissue
reconstruction. Newer flaps such as the medial
sural artery perforator flaps are increasing in
popularity
• The fibula free flap is now considered
the workhorse for mandibular reconstruction fol-
lowing ablative surgery. Planning software
makes osteotomies easier
• The deep circumflex iliac artery with internal
oblique provides a superior form for the mandible
and facilitates deeper implant placement and
should be considered if implant-retained oral
rehabilitation is planned
• The scapula provides a good option for extensive
soft tissue resections including the mandible and
an alternative if atheroma precludes use of the
fibula. The donor site is also the best tolerated
Midface and maxilla
• Multidisciplinary decision-making should include
the patient, surgeon and dental prosthodontist
• Prosthetic options reduce the morbidity of treat-
ment and can give excellent results but recon-
structive options should be considered as the
defect becomes larger and more complex
Oropharynx
• Using local tissue only to restore the constrictor
tube is essential. Free tissue transfer is best
reserved for the reconstruction of the soft palate
• Functional results for posterior tongue reconstruc-
tion are disappointing
• The greater role played by transoral surgery will
reduce the need for reconstruction in this area
Pharyngolarynx
• Partial pharyngeal defects may be closed primarily
or using a pedicled myocutaneous, usually a pec-
toralis major flap or with a free flap
• Total circumferential defects where the lower ana-
stamosis is above the clavicle can be reconstructed
with several free flaps. In previously untreated
patients, anterolateral thigh free flaps, tubed over
a salivary bypass tube, appear to carry lowest
complication rates. In post-radiotherapy patients,
limited evidence suggests that gastromental free
flaps may have some advantages
• Tubing over and use of a salivary bypass tube
appears to decrease complication rates with
anterolateral thigh and radial forearm free flaps
• Total circumferential defects where the lower
anastamosis is below the clavicle may be recon-
structed by gastric pull through or colonic
transposition
RECONSTRUCTIVE CONSIDERATIONS IN HEAD AND NECK SURGICAL ONCOLOGY: UK GUIDELINES
Salvage laryngectomy
• Use of vascularised tissue to buttress or augment the
pharynx in patients undergoing salvage total laryn-
gectomy reduces pharyngocutaneous fistula rates
Acknowledgment
The authors acknowledge the contributions of Stephen
Morley to the previous edition of this manuscript.
References
1 Hanasono MM, Matros E, Disa JJ. Important aspects of head
and neck reconstruction. Plast Reconstr Surg 2014;134:
968e–80e
2 Cannady SB, Lamarre E, Wax MK. Microvascular reconstruc-
tion: evidence-based procedures. Facial Plast Surg Clin North
Am 2015;23:347–56
3 Soutar DS, McGregor IA. The radial forearm flap in intraoral
reconstruction: the experience of 60 consecutive cases. Plast
Reconstr Surg 1986;78:1–8
4 Chana JS, Wei FC. A review of the advantages of the anterolat-
eral thigh flap in head and neck reconstruction. Br J Plast Surg
2004;57:603–9
5 Markiewicz MR, Bell RB, Bui TG, Dierks EJ, Ruiz R, Gelesko
S et al. Survival of microvascular free flaps in mandibular recon-
struction: a systematic review and meta-analysis. Microsurgery
2015;35:576–87
6 Wallace CG, Chang YM, Tsai CY, Wei FC. Harnessing the
potential of the free fibula osteoseptocutaneous flap in mandible
reconstruction. Plast Reconstr Surg 2010;125:305–14
7 Collin T, Sugden P, Ahmed O, Ragbir M. Technical considera-
tions of fibular osteocutaneous flap dissection. J Plast Reconstr
Aesthet Surg 2008;61:1503–6
8 Brown JS, Barry C, Ho M, Shaw RJ. A new classification of the
mandibular defect based on a systematic review of segmental
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resection and composite microvascular reconstruction. Lancet
Oncol 2016;17:e23–30
9 Brown JS, Shaw RJ. Reconstruction of the maxilla and
midface: introducing a new classification. Lancet Oncol 2010;
11:1001–8
10 Brown JS, Zuydam AC, Jones DC, Rogers SN, Vaughan ED.
Functional outcome in soft palate reconstruction using a radial
forearm free flap in conjunction with a superiorly based pharyn-
geal flap. Head Neck 1997;19:524–34
11 Kim EK, Evangelista M, Evans GR. Use of free tissue transfers in
head and neck reconstruction. J Craniofac Surg 2008;19:1577–82
12 Patel RS, Goldstein DP, Brown D, Irish J, Gullane PJ, Gilbert
RW. Circumferential pharyngeal reconstruction: history, critical
analysis of techniques, and current therapeutic recommenda-
tions. Head Neck 2010;32:109–20
13 Sarukawa S, Asato H, Okazaki M, Nakatsuka T, Takushima A,
Harii K. Clinical evaluation and morbidity of 201 free jejunal
transfers for oesophagopharyngeal reconstruction during the
20 years 1984–2003. Scand J Plast Reconstr Surg Hand Surg
2006;40:148–52
14 Varvares MA, Cheney ML, Gliklich RE, Boyd JM, Goldsmith
T, Lazor J et al. Use of the radial forearm fasciocutaneous free
flap and montgomery salivary bypass tube for pharyngoesopha-
geal reconstruction. Head Neck 2000;22:463–8
15 Paleri V, Drinnan M, van den Brekel MW, Hinni ML, Bradley
PJ, Wolf GT et al. Vascularized tissue to reduce fistula following
salvage total laryngectomy: a systematic review. Laryngoscope
2014;124:1848–53
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Address for correspondence:
Maniram Ragbir,
Newcastle upon Tyne Hospitals NHS Foundation Trust,
Newcastle upon Tyne, UK
E-mail: Maniram.Ragbir@nuth.nhs.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S198–S207. GUIDELINE
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reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000633

Palliative and supportive care in head and neck

cancer: United Kingdom National Multidisciplinary
Guidelines

H COCKS1, K AH–SEE2, M CAPEL3, P TAYLOR4

1
ENT Department, City Hospitals Sunderland, Sunderland, 2Department of Otolaryngology – Head and Neck
Surgery, Aberdeen Royal Infirmary, Aberdeen, 3George Thomas Hospice Care, Ty George Thomas, Park Road,
Whitchurch, Cardiff, and 4St Benedict’s Hospice, Sunderland, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. It provides recommendations on the assessments and interventions for this group of patients
receiving palliative and supportive care.

Recommendations
• Palliative and supportive care must be multidisciplinary. (G)
• All core team members should have training in advanced communication skills. (G)
• Palliative surgery should be considered in selected cases. (R)
• Hypofractionated or short course radiotherapy should be considered for local pain control and for painful bony
metastases. (R)
• All palliative patients should have a functional endoscopic evaluation of swallowing (FEES) assessment of
swallow to assess for risk of aspiration. (G)
• Pain relief should be based on the World Health Organization pain ladder. (R)
• Specialist pain management service involvement should be considered early for those with refractory pain. (G)
• Constipation should be avoided by the judicious use of prophylactic laxatives and the correction of systemic
causes such as dehydration, hypercalcaemia and hypothyroidism. (G)
• Organic causes of confusion should be identified and corrected where appropriate, failing this, treatment with
benzodiazepines or antipsychotics should be considered. (G)
• Patients with symptoms suggestive of spinal metastases or metastatic cord compression must be managed in
accordance with the National Institute for Health and Care Excellence guidance. (R)
• Cardiopulmonary resuscitation is inappropriate in the palliative dying patient. (R)
• ‘Do not attempt cardiopulmonary resuscitation’ orders should be completed and discussed with the patient
and/or the family unless good reasons exist not to do so where appropriate. This is absolutely necessary
when a patient’s care is to be managed at home. (G)

Introduction term – even lifelong for survivors. In addition to the

Palliative care aims to improve the quality of life (QoL)
of patients and their carers facing the problems asso-
ciated with life threatening illness. This can be achieved
by the prevention and relief of suffering, ensuring
comfort and dignity, by means of early identification,
assessment and management of pain and other, physical,
psychosocial and spiritual issues.
Patients with head and neck cancer are a group in
whom both specialist palliative and supportive care is
especially appropriate whether the treatment intent is
curative or not, since the disease and its treatments
result in a huge burden of morbidity: short and long
physical symptoms, these patients often have very sig-
nificant comorbidities, including tobacco and alcohol
dependence, and complex psychosocial issues.
All professionals caring for head and neck cancer
patients should assess palliative and supportive care
needs in initial treatment planning, and throughout
the illness, and be aware when specialist palliative
care expertise is needed. This may involve core multi-
disciplinary team (MDT) members, social workers,
psychologists etc. Levels of intervention may involve
in-patient, out-patient, day care, home care and tele-
phone advice, from a single, arm’s length intervention
PALLIATIVE AND SUPPORTIVE CARE IN HEAD AND NECK CANCER: UK GUIDELINES
to a taking over of care. Support provided will need to
accommodate any communication impediment. In turn,
specialist palliative care practitioners need to be aware
of when and how to use palliative interventions such as
surgery, radiotherapy (RT) and chemotherapy. All this
is best achieved by a high level of integration of ser-
vices – team working, including the primary care
team – and excellent communication, with the ‘key
worker’ (usually a specialist nurse) at the centre.
BOX I
MAIN TARGETS FOR PALLIATIVE CARE
INTERVENTIONS IN HEAD AND NECK CANCERS
Medical and surgical treatments
Pain
Hydration and nutrition
Gastrointestinal symptom relief
Anxiety
Agitation
Dysphagia
Dyspnoea
Bleeding
Airway management
Hypercalcaemia
Holistic, psychosocial and complementary
Breaking bad news
Patient aspirations and expectations
Anxiety
Counselling
Psychological support
Emotional support
Support groups
Massage therapy
Aromatherapy
Recommendation
• Palliative and supportive care must be
multidisciplinary (G)
Approaches
Palliative care takes a holistic approach, addressing phys-
ical, psychological, social and spiritual needs of the
patient, their carers and family (Box I). Interventions
which may be appropriate to palliative care include onco-
logical and surgical approaches, drug management, psy-
chological support, Allied Health Professional (AHP)
input and complementary therapies. This paper focuses
on medical and surgical interventions for physical symp-
toms, but these should be addressed as part of a wider
S199
holistic and multidisciplinary approach, which includes
concern with psychosocial and spiritual issues.1–3
Whilst the distinctions between physical and psycho-
social symptoms should not be overstated, different
interventions will dominate in each category. Drugs,
anticancer treatments such as RT, surgery and proce-
dures will dominate in the first category, whilst coun-
selling, honest communication, support groups and
complementary therapies will be preferred in the
second. This distinction is not clear-cut, however;
counselling and honest communication are important
parts of pain relief, whilst drugs have a role in the man-
agement of symptoms such as anxiety and depression.
A well-developed multidisciplinary approach, coupled
with an open-minded approach to intervention, is there-
fore essential.
It is the role of the MDT team to discuss treatment
options in all patients. This includes decisions on
who should be treated and what is untreatable
disease. This is a complex issue and although broad
guidelines can be applied each case should be assessed
individually. Radical treatment in advanced or recur-
rent head and neck cancer may be futile and result in
poorer QoL, therefore important decisions need to be
made at presentation about which treatment pathway
to take. The alternative where there is a low chance
of cure is a palliative pathway. Palliative treatments
include surgical and non-surgical interventions with
the intention of slowing disease growth and symptom
control, and extending life with focus purely on
symptom control.
Effective decision making in the palliative setting is
important. The patient and family should adequately
understand the diagnosis and prognosis, especially if
the trajectory changes due to intervention or disease
progression. It should be made clear that symptoms
will be identified and treated and patients should be
asked if there are any new goals for their treatment
since cure is not possible. In other words, the team
should not convey a sense of hopelessness simply
because the goal is not indefinite survival. Hope can
be maintained within the context of the patient’s own
goals whether they are:
• physical – relief of symptoms
• psychological – fear of distress, suffocation,
bleeding or uncontrollable pain at the end of life
• Social – desire to witness a family event, celebrate
a birthday or make a trip.
Symptoms should be actively sought and treated in a
proactive manner, and it should not be assumed or con-
veyed that any new symptom is as uncontrollable as the
tumour itself. Treatment options should be discussed
for the new symptom including those that may not
extend life. Although patient choice is central to the
treatment options taken, the treating clinician should
make recommendations to guide treatment and share
the burden of difficult decisions.
S200
Recommendation
• All core team members should have training
in advanced communication skills (G)
Symptom control
Surgical palliation
Incurable end-stage head and neck cancer leads to distres-
sing symptoms. Patients may remain active and self-
caring while trying to cope with problems of pain, swal-
lowing, breathing and bleeding. Palliative surgery may be
indicated in such cases. Little high-level evidence is avail-
able to confirm the surgical benefit; however, descriptive
studies support its use in selected cases. Surgery can
reduce primary tumour bulk, reduce pain and bleeding,
improve swallowing, nutrition and improve and airway
(see below). Debulking surgery for advanced neck
disease can achieve symptom control, but major resec-
tions only rarely offer levels of benefit, which justify
the extent of surgical morbidity.
Newer endovascular techniques, including embol-
isation and vessel stenting, may offer symptom
control for bleeding related to major vascular erosion,
and these interventions can be considered in patients
at high risk of erosion of major vessels.
Acute haemorrhage from carotid ‘blow-out’ (erosion
of the carotid vessels) is a distressing end of life event.
Whilst occasional success can be achieved with swift
surgical intervention, many patients succumb rapidly.
In these cases, attempts to reduce the flow of blood
with direct pressure while administering appropriate
rapid acting sedatives (e.g. benzodiazepines) should be
made. Constant verbal support to the patient is a key
to help handle anxiety. Do not leave the patient’s side.
If surgical intervention is considered inappropriate
careful discussion and measured information giving
to the patient (if they wish to participate) or family
members and carers is essential. This should include
the anticipated clinical scenario and an acceptable plan
of care should be devised to manage these circumstances.
This may include the use of dark towels, anticipatory
prescribing, and may influence preferred place of care.
Recommendations
• Palliative surgery should be considered in
selected cases (R)
• For control of bleeding endovascular stenting
or embolisation should be considered (R)
Non-surgical palliation
Radiotherapy. Debate continues around the optimal
dosage regimen for palliative RT. Low-level evidence
exists for the use of hypofractionation schedules and
H COCKS, K AH SEE, M CAPEL et al.
short course RT. Other protocols such as those
described by the Radiation Therapy Oncology Group
have also demonstrated benefit. Symptom control can
be achieved in up to 80 per cent of selected patients
with particular response in terms of pain control. No
high-level evidence exists to support one protocol
over another, but case series report benefit. Re-irradi-
ation may be offered but may be associated with
severe radiation toxicity.
A systematic review of RT for painful bone metasta-
ses reports benefit in up to 50 per cent of patients.4
There is evidence to support the use of bisphospho-
nates to aid pain control of bone pain as an additional
step once RT and conventional pharmacology has
been used. The role of the new monoclonal drugs
including RANK – ligand inhibitors (e.g. denosumab)
has yet to be elucidated.
Chemotherapy. This includes the use of platinum-based
agents, 5-fluorouracil and methotrexate, either as mono-
therapy or in combination with RT and demonstrates
benefit in symptom control and QoL measures, but may
increase toxicity and hence side effects from the treat-
ment. Careful consideration of the balance between
benefit and harm must be made on an individual patient
basis. Non-platinum-based agents are reported as confer-
ring symptom control in the selected cases.
Future modalities. Future research will include the role
of taxanes, e.g. paclitaxel, monoclonal antibodies e.g.
cetuximab, newer chemotherapeutic agents, photo-
dynamic therapy and interstitial laser therapy.
Descriptive series report some symptom controls
using these modalities but without any evidence of
improved survival.
Recommendations
• Hypofractionated or short-course RT should
be considered for local pain control and for
painful bony metastases (R)
• Bisphosphonates can be considered for bone
pain following RT (R)
Palliation of dysphagia
Forty per cent of patients with head and neck cancer
suffer from dysphagia. This is due to:
• mechanical obstruction
• functional obstruction
• drug induced side effects
• fistula
• pain.
Assessment of the swallow is essential in palliative head
and neck patients. It is important to establish whether oral
intake is possible and whether it is safe. Aspiration is not
PALLIATIVE AND SUPPORTIVE CARE IN HEAD AND NECK CANCER: UK GUIDELINES
uncommon and may be silent in up to 40 per cent of
patients, thus the bedside assessment is of limited value.
Functional endoscopic evaluation of swallowing (FEES)
is straightforward, easily repeatable, portable and can
give good information on the aetiology of aspiration as
well as feedback to the patient on trials of preventative
manoeuvres. It can also be useful in the assessment of
ability to deal with different textures and complements
information obtained from videofluoroscopy.
Aspiration does not inevitably mean no oral intake.
A degree of aspiration may be well tolerated and
methods taught to clear the airway after swallowing
can be implemented. Similarly certain textures may
be better tolerated and the use of thickened fluids can
help maintain oral intake. It is important to take into
account the patient’s wishes and the patient may
make an informed choice to continue to swallow
despite the potential and real risk of aspiration pneumo-
nia. Quality of life is absolute.
In patients who are unable to swallow, the use of an
enteral route via nasogastric tube (NGT) or gastrostomy
allows for hydration, nutrition and medication. The type
of tube used depends largely on ability to pass an NGT
or fashion a gastrostomy, perceived duration of use and
patient choice. If enteral nutrition via NGT is likely to
extend beyond two to three weeks then gastrostomy
should be considered and discussed with the patient.
There exists no clear guidance on when or if it is
acceptable to withdraw nutritional support. Patient
and family wishes are crucial in this decision process
and full consultation is imperative.
Conventional treatments can be helpful in the palli-
ation of swallowing. Surgical debulking either with or
without the laser or debrider and RT may help reduce
bulk in a hypopharyngeal tumour, dilatation can help in
stricture formation and this can be surgical or radiologic-
ally guided. Stenting may play a role but often head and
neck tumours are too high to accommodate a stent com-
fortably and without impacting on other functions.
Recommendations
• All palliative patients should have a FEES
assessment of swallow to assess for risk of
aspiration (G)
• Establishment of enteral feeding must be
considered early in patients who are unable to
maintain their intake orally (G)
Palliation of the airway
Where there is airway compromise it is common prac-
tice to consider a tracheostomy. However, it may be
possible to avoid tracheostomy in some cases if the
consideration is given to surgical debulking techniques.
This is dependent on local expertise and equipment.5
Sometimes avoiding surgical intervention is the most
appropriate course of action, for example, a patient with
S201
a tracheal tumour that has been repeatedly debulked,
and has received palliative RT, is not a candidate for
stenting. There will come a time when the airway com-
promise will be life threatening. A tracheostomy may
not be an option in this instance. In such instances
opioids for dyspnoea in addition to palliative sedation
and reduction of secretions can support a patient in a
terminal event.
These situations are difficult and information should
be imparted to the patient sensitively. In the situation
where the patient wants to fully discuss the anticipated
scenario a sense of control can be restored to them by
discussing what interventions can be undertaken
pharmacologically to avoid any distress. If the patient
does not want to participate in the discussion this
should be documented and discussed with family
and/or carers. This situation may influence the pre-
ferred place of care. To have the patient and the
family prepared for the event is paramount. They
must know what will be in place to prevent the dys-
pnoea and anxiety associated with such a situation
and the patient must be comfortable to the end.
If a tracheostomy is indicated local protocols should
exist or be developed to help the patient, the family and
community staff manage tracheostomy wound care
along with maintenance of a clean secure tube. Heat
moisture exchange and voicing attachments may be
used to aid patient communication.
Pain
Pain is very common, affecting most patients at any
stage. It may be disease or treatment related, either
acute and/or immediate or persistent and/or lifelong.
Pain occurring after a long, pain free interval is likely
to be recurrent disease. Assessment must take account
of the presence of ‘total pain’ i.e. physical, spiritual,
psychological and social elements. The three major
pain types are all encountered – somatic, visceral
and, particularly difficult, neuropathic.
Analgesic use is best based on the World Health
Organization (WHO) ‘pain ladder’ (Box II) with
three steps of increasing potency, and used depending
on pain severity and response. The severity of the
pain dictates the strength of the analgesic and the patho-
physiology dictates the adjuvant used.
BOX II
WHO PAIN LADDER
Paracetamol ± non-steroidal anti-inflammatory
drug ± adjuvant
Weak opioid (codeine or tramadol) + step 1 drugs
Strong opioid replacing the weak + step 1 drugs
The choice of formulation depends on whether the
patient can swallow, is vomiting, or has a nasogastric
(NG) or gastrostomy tube in situ.
S202
Somatic pain. Morphine remains the first choice strong
opioid, other than perhaps in renal impairment when an
alternative is preferred. It is initiated by titrating imme-
diate release morphine oral solution or tablet (e.g.
Oramorph™ solution or Sevredol™ tablet). Once
responsiveness and dosage are known, then sustained
release preparations are used, with immediate release
doses for breakthrough at a sixth of the 24 hour sus-
tained release dosage. If the patient can swallow, then
sustained release tablets (e.g. MST Continus™) or cap-
sules (e.g. Zomorph™) can be used. If a tube is in place
then a morphine suspension (e.g. MST suspension™)
or opened capsules (e.g. Zomorph™) can be used. If
this is not feasible, usually because of vomiting, then
a subcutaneous (SC) infusion of morphine or diamor-
phine can be used, with SC doses for breakthrough.
Diamorphine is preferred since it is more soluble and
can be used in much smaller volumes.
Transdermal preparations of fentanyl have theoretical
and practical attractions for stable background pain as an
alternative, particularly if there is morphine intolerance
(e.g. sedation and dysphoria) or there is renal failure.
For breakthrough pain, oral opioids can still be used.
Alternatively, new preparations of buccal, sublingual
or intranasal fentanyl may have a role in specific situa-
tions, with supervision of a specialist service.
Oxycodone can be an alternative to morphine where
there is intolerance, particularly dysphoria; there is an
immediate release solution and injection, but there is
only a tablet form of sustained release oral preparation,
limiting its use where swallowing is compromised.
Hydromorphone is not useful orally where swallowing
is impossible, both immediate and sustained release
being capsules, but it may be injected. Methadone in
liquid form can be very useful, being rapid in onset
and long acting because of its half-life; it is best used
by specialists as it can accumulate.
Neuropathic pain. This is very common both as a pre-
senting feature of the disease and a result of treatment,
particularly radiation. The drugs used can be referred to
as adjuvants.
• A tricyclic antidepressant, most usually amitriptyl-
ine is available as tablet and liquid.
• Anticonvulsants such as gabapentin and pregaba-
lin are the most used, available only as tablets or
capsules unless through special arrangements
with a pharmacy. Gabapentin can be opened and
administered via the gastrostomy tube.
• Carbamazepine is an alternative and is available
both as tablet, liquid and even suppositories.
Sodium valproate is also available as a liquid
preparation.
First line would be either antidepressant or anticon-
vulsant titrated to maximum dose tolerated (usually
added to a conventional analgesic): second line
would be to use both.
H COCKS, K AH SEE, M CAPEL et al.
Some advocate corticosteroids (e.g. dexamethasone
8–16 mg daily) as first line for acute neuropathic
pain where there is felt to be a significant inflammatory
component. Appetite stimulation limits use if dyspha-
gia is a concomitant feature. It is not for chronic or pre-
dictably long-term pain. Clonazepam is occasionally
useful. Methadone and ketamine are useful, but only
in specialist settings.
Visceral pain. Treatment depends on the cause, titrating
analgesics and using the pain ladder. If the pain is
poorly sensitive to opioids, adjuvants should be consid-
ered early, for example pain due to metastatic disease in
the liver or nerve compression may be eased with
Dexamethasone (4–8 mg daily).
Judicious use of all these drugs is best achieved by
seeking advice from the specialist palliative care
service whenever there is concern. Interventional pain
techniques can be very effective where systemic treat-
ments fail or if the patient is intolerant of the significant
doses of combination analgesics.
Mucosal pain. This can be due to treatment, infection or
tumour. Treatment of infection such as candida
or herpes is essential. Useful additional topical agents
include sulcralfate, benzydamine, chlorhexidine, ster-
oids and topical local anaesthetics such as lignocaine
preparations. Coating measures including bioadherent
oral gel may be preferred by the individual patient.
Recommendations
• Pain relief should be based on the WHO pain
ladder (R)
• Specialist pain management service
involvement should be considered early for
those with refractory pain (G)
Nausea and vomiting
The approach must take an account of the large number
of patients who are enterally fed. Even with this there is
often a need for injectable anti-emetics – subcutaneous
(SC) boluses or continuous infusions, at least until
initial control is established.
Enteral feeding poses its own challenge, and pro-
kinetic drugs such as metoclopramide (tablet, oral solu-
tion or injection) or domperidone (tablet, suspension or
suppository) may be needed to ensure best function.
Otherwise the approach is similar to that in general
use. Remember the practical issue of providing a
large bowl, tissues and water for the patient and be pre-
pared to rehydrate using IV or SC fluids if appropriate.
Constipation
Constipation develops in half of patients who are ter-
minally ill with cancer admitted to a hospice. In
PALLIATIVE AND SUPPORTIVE CARE IN HEAD AND NECK CANCER: UK GUIDELINES
addition, it is common during treatment in many
patients. This is due to dehydration, reduced physical
activity and the use of constipating drugs, particularly
opioids and anticholinergic medication. Laxatives
should be initiated once opioid medication is pre-
scribed. Hypercalcaemia and hypothyroidism are
other causes, which may be overlooked.
The principle of treatment is avoidance and early rec-
ognition. Enquiry should be made on patient contact.
Laxative agents include stimulants such as bisacodyl
and senna and softeners such as lactulose, magnesium
hydroxide and docusate. Polyethylene glycol prepara-
tions including movicol and laxido are commonly
used. These should be used prophylactically. If consti-
pation develops it can lead to nausea and vomiting and
in the severe situation pseudobstruction. If rectal exam-
ination reveals hard stool then the use of suppositories
and enemas can be helpful. Ultimately, a manual
evacuation may be necessary.
Recommendation
• Constipation should be avoided by the
judicious use of prophylactic laxatives and the
correction of systemic causes such as
dehydration, hypercalcaemia and
hypothyroidism (G)
Confusion and agitation
It is important to distinguish anxiety (unsettled, frigh-
tened, panic) from confusion, particularly delirium.
Confusion is common, affecting up to 75 per cent of
cancer patients at some stage. Many head and neck
patients have a history of heavy alcohol (and tobacco)
consumption, predisposing them to the effects of
withdrawal, and given that cancer is more commonly
seen in old age; then cognitive impairment is not
uncommon.
Benzodiazepines are the mainstay of pharmacologic-
al treatment of anxiety. Diazepam can be given orally,
via a tube in liquid form, or by injection intravenously.
Lorazepam can be swallowed or a tablet dissolved sub-
lingually. If injections and/or infusions are needed,
midazolam is preferred, as it can be given subcutane-
ously (most common route) or intravenously when
almost immediate effect is needed. The key limiting
factor, however, is rapidly developing tolerance; ben-
zodiazepines are useful for short-term management of
episodes of anxiety, but are limited where anxiety is
pre-existing and established.
Delirium as a cause of confusion can be related to a
number of organic causes – infection, dehydration,
metabolic disturbance, respiratory failure, urinary reten-
tion, constipation, brain metastases, etc. Administered
drugs are common causes, particularly opioids and
drug withdrawal (see above). While treatment has to
be aimed at the cause, symptom management is required
in the short term. While benzodiazepines have a role,
S203
indeed a specific indication in drug withdrawal, most
often delirium is better managed using haloperidol (as
tablet, liquid or injection, including SC) or levomepro-
mazine (as tablet or injection) where sedation is
needed in managing paranoia etc.
In some cases, particularly for irreversible agitation
or delirium in a dying patient, benzodiazepines and
antipsychotics need to be combined and are often admi-
nistered using a syringe driver.
Recommendation
• Organic causes of confusion should be
identified and corrected where appropriate,
failing this, treatment with benzodiazepines
or antipsychotics should be considered (G)
Secretions
Although xerostomia is common in these patients,
excess secretions and/or the inability to swallow or
otherwise clear secretions is often troublesome.
Physically the use of suction either by carer or the
patient is often helpful.
There are three widely used antimuscarinic drugs.
• Hyoscine hydrobomide (scopolamine) is available
as a transdermal patch, oral or sublingual tablet
and is commonly used; however, it has central
as well as peripheral actions and (unpredictable)
sedation and/or confusion can result.
• Hyoscine butylbromide, which is not central
nervous system active, but equally effective per-
ipherally, and is arguably the drug of choice. It
is available as a tablet, though often ineffective
by that route; hence SC use may be preferred.
• Glycopyrronium, which is similarly peripherally
active, and is most often given subcutaneously.
A liquid form can be prepared but efficacy is
unpredictable.
• Excess secretions at the end of life are treated simi-
larly, but the evidence in a Cochrane review sug-
gests they are of very limited benefit. Established
practice accepts SC preparations of anticholinergic
medication are available for use to support this end
of life phase. Timely management is a key here; if
secretions develop, then regular or continuous
antisecretory drugs should be started as soon as
practical, rather than relying on PRN drugs.
Steroids
As with other cancers, corticosteroids are widely used.
Dexamethasone (Table I) is the most used, because of
its potency, relative lack of mineralocorticoid properties,
and wide range of formulations (water soluble tablets,
solution, and injection, SC or intravenous).6
Dexamethasone 1 mg = Prednisolone 7.5 mg
S204
TABLE I
INDICATIONS AND DOSAGE FOR STEROID
(DEXAMETHASONE) USE
Appetite, energy and wellbeing 4 mg initially
Adjuvant analgesic 8–16 mg initially
Anti-emetic See above
Spinal cord compression See NICE
guidelines7
Tumour oedema (e.g. tracheal compression, 8–16 mg initially
superior vena cava obstruction)
Long-term use also requires that attention be paid to
bone mineral density, and bisphosphonates, and
calcium and/or vitamin D supplements are indicated.
BOX III
SPINAL METASTASES
Type of associated pain
Pain in spine (new or progressive)
Spinal pain aggravated by straining
Localised spinal tenderness
Pain in spine at night preventing sleep
Neurological symptoms and signs
Radicular pain
Limb weakness
Difficulty walking
Sensory loss
Bladder or bowel dysfunction
Signs of caudal equina/spinal cord compression
If used for any length of time patients must carry a ‘steroid
card’, keep it up to date, and be aware of the advice on it,
i.e. to increase the dose when there is intercurrent illness
or other stressor; and the need to reduce very gradually if
used for more than three to four weeks – including at the
end of life. Some advise that steroids given for poor appe-
tite or fatigue can be discontinued then. This puts the
patient at risk of steroid insufficiency, an unnecessary
symptom burden even at that stage, and dexamethasone
can be given in small volumes subcutaneously once
daily, as part of end of life care if appropriate.
Spinal metastases
The incidence of spinal metastases in head and neck
squamous cell carcinoma is reported to be less than 2
per cent; however, it is more common in thyroid
cancer (2–13 per cent). The most important factor in
determining outcome is neurological status prior to
treatment. Due to the devastating neurological sequelae
of spinal cord or cauda equina compression early rec-
ognition (Box III) and action is essential and consider-
ation that symptoms may be suggestive of spinal
metastatic disease is the first step.7
Neurological symptoms and signs should be
assessed and a magnetic resonance imaging of the
H COCKS, K AH SEE, M CAPEL et al.
whole spine obtained. This is an oncological emer-
gency and steroids should be commenced while inves-
tigations or admission are arranged. Treatment depends
on findings and includes steroids, surgical stabilisation
and RT. Clear guidelines on diagnosis and manage-
ment have been published by National Institute for
Health and Care Excellence (NICE) and the readers
should familiarise themselves with these.7
Recommendation
• Patients with symptoms suggestive of spinal
metastases or metastatic cord compression
must be managed in accordance with the
NICE guidance (R)
Care of the dying
Care of the dying is an important part of good palliative
care. Dying patients may have significant and rapidly
changing symptoms, together with a recognition that
no further active intervention is appropriate. For these
reasons, timely assessment, regular review and confi-
dent symptom control are essential. In addition, this
is an important time for loved ones; as noted by
Dame Cicely Saunders, ‘How people die remains in
the memories of those who live on’. Ongoing sensitive
and honest communication, coupled with sensible and
proactive decision-making are therefore essential.8
Reversible causes for a patient’s deterioration should
be considered and may be acted upon depending upon
earlier discussions, clinical acumen and based on the
best interests of the patient. The physical changes pre-
ceding death generally include decreasing mobility,
decreasing level of consciousness and interaction,
minimal intake, progressing to no oral intake, decreasing
urine output, haemodynamic deterioration and changes
in respiratory pattern. Recognising death is imminent,
the doctor may lead multiprofessional decision making
and communication ensuring the patient (if appropriate)
and families or carers understand the expected trajectory.
The patient’s values and preferences should be
upheld where possible, these may include rapid dis-
charge to enable the patient to die in the place of
their choice, or enable their family to stay with them
if in in-patient settings. Any religious, spiritual or cul-
tural preferences should be identified.
The Liverpool Care Pathway (LCP) was a protocol
developed at the Marie Curie Institute Liverpool, and in
use in the UK between 1997 and 2014. Concerns about
the use of the pathway were raised in the press, and a sub-
sequent government review was undertaken. Whilst
recognising both good and bad outcomes arising from
the use of the pathway, the ultimate recommendation of
the review body was that the LCP be withdrawn.
Current approach is based on this framework but using
a more individualised and tailored care plan. Such
plans are currently subject to local variation but can be
PALLIATIVE AND SUPPORTIVE CARE IN HEAD AND NECK CANCER: UK GUIDELINES
used in all care settings including patient homes. National
guidance is being developed following consultation.
A key role of the doctor is to recognise that death is
imminent, and, as recommended in the government
review, the patient’s senior clinician has a vital role
in this decision in the MDT. Recognition of dying
should prompt a thorough review of all care and inter-
ventions, with unnecessary medication being stopped,
and essential medication continued, usually by SC
infusions and boluses. In the head and neck patient,
the frequent presence of NG and gastrostomy tubes
allows continued use of some medications which
would otherwise be impossible to administer.
It is important to highlight that recognising dying
does not automatically lead to discontinuing any such
interventions; only that their role in improving symp-
toms should be assessed.
Whilst nutrition is usually inappropriate in dying
patients neither SC nor intravenous fluid is necessarily
ruled out – although the benefits can be, indeed often
are very limited. Enteral tubes provide a further
option for those patients.
Sensitive discussion with the patient (if appropriate)
and family or carers should be initiated to dispel any
concerns held and agree a plan appropriate to the indi-
vidual which may require modification depending
upon the timescale and symptoms observed. A
further vital aspect of end of life care, recognised
both in the LCP and the review, is the need for
regular multiprofessional assessment, and the possibil-
ity that patients may improve, for whatever reason, and
hence the management plan be changed.
Whilst an individualised approach is vital for dying
patients, certain symptoms are common enough to
warrant ‘anticipatory prescribing’. The four major
symptoms for which this is appropriate are:
• pain
• nausea and vomiting
• agitation
• excess secretions.
The choice of drugs used is left to individual units
and must be individualised further for some patients.
For most purposes:
• analgesia – diamorphine or morphine
• anti-emetic – haloperidol or levomepromazine
• agitation – midazolam and/or levomepromazine
or haloperidol
• antisecretory – hyoscine, either butyl or
hydrobromide.
Common reasons for modifying the drugs of choice
include poor tolerance of previous drugs, cases where
other drugs have an already-established role, clinical
contra-indications or renal failure. Fortunately, all the
commonly needed drugs can be given subcutaneously,
and feeding tubes increase the available options. Areas
S205
which require ongoing monitoring and vigilance
include mouth care, tracheostomy and wound care,
pressure areas, and continence.
Recommendation
• All patients at the end of life should have
anticipatory medication available to palliate
common symptoms and should have an
individualised care plan (G)
Do not attempt resuscitation (DNAR)
(cardiopulmonary resuscitation (CPR))
This is a subject of such wide clinical and ethical com-
plexity (Box IV and V) that it is not possible to offer
more than a few thoughts on the main points. Such a
decision applies ONLY to the state of cardiopulmonary
arrest – it does not imply withholding other treatments,
including other ‘resuscitation’ measures (e.g. reinsert-
ing a dislodged tracheostomy tube).
BOX IV
FUNDAMENTAL ETHICAL PRINCIPLES
Respect for autonomy
Beneficence
Non-maleficence
Justice
BOX V
RELEVANT ARTICLES OF HUMAN RIGHTS ACT
The right to life
Freedom from inhuman or degrading treatment
The right to privacy
Freedom of expression and to be informed
Freedom from discrimination
When considering palliative and end of life care, one
specific area for consideration is that of CPR.
Ultimately, any decisions made around CPR should
be undertaken in advance. In the event of a cardiac
arrest, and where no such decisions have been made
in advance, the default position is to perform CPR. In
some cases, even in patients with incurable disease,
this is appropriate. In the dying patient, however, or
in cases where the chances of CPR succeeding are
remote, then CPR adds no benefit to patient care. In
such cases, a ‘Do not attempt cardiopulmonary resusci-
tation’ (DNACPR) order should be completed.
There exists a number of issues regarding DNACPR
decisions, outlined in national guidance issued by the
British Medical Association (BMA), Royal College
of Nursing (RCN) and Resuscitation Council (RC),
S206
and recently examined in a Court of Appeal Judgement.
Two key points stand out – the decision-making
around CPR, and the discussion around such decisions.
The current BMA, RCN and RC guidance is sum-
marised here, but may be subject to review in the
coming months.
Decisions around CPR
Where a cardiac arrest is a significant possibility, where
CPR has a reasonable chance of success, and where
no advance decisions have been made with respect
to resuscitation, then CPR should be attempted.
Examples of such cases include acute reversible ill-
nesses or treatable arrhythmias. Similarly, if a cardiac
arrest is unlikely, then CPR should be attempted if it
occurs. Examples here include the otherwise healthy
person admitted with a relatively minor illness or an
out-of-hospital arrest in public. A presumption of
patient consent exists here, and it is not relevant to
discuss in advance unless requested (and in such a
case, patient wish should be respected). Whilst this is
applicable to many hospital patients, it is less relevant
to palliative care patients, in whom life-threatening
events are more likely, and CPR is less likely to
succeed.
At the other extreme, where a patient is dying and no
reversible causes for their condition exist, then CPR is
inappropriate. In this context, cardiac arrest may be
viewed as the final event in the process of natural
death. Nevertheless, whilst the clinical decision may
be clear, serious consideration needs to be given to dis-
cussion with the patient and family; this is covered in
the section ‘Discussing CPR decisions’, below.
In many cases, including in palliative care, the ben-
efits and burdens of CPR are less clear-cut. For
example, in a patient with an ultimately palliative diag-
nosis but who is otherwise active and well, there is a
small chance that CPR in the event of a cardiac arrest
may succeed. It is beyond the remit of this work to
outline factors that count for and against this. In such
cases, the preferences of patients (or those delegated
to make decisions on their behalf) are pivotal.
Discussing CPR decisions
As outlined above, discussing CPR decisions is not
relevant in a large proportion of hospital patients, as
presumption of consent exists. This section is con-
cerned with those cases where cardiac arrest is a realis-
tic possibility.
Where CPR would not succeed. In cases where it has
been determined clinically that CPR has no realistic
chance of success, the decision rests with the medical
team. Any discussion revolves around sensitively
informing the patient (and/or any person delegated to
be involved in such discussions) of the decision that
has been made. Difficulties here arise where the
patient or delegated person objects to the decision. In
such cases, seeking a second opinion is good practice.
H COCKS, K AH SEE, M CAPEL et al.
It is usually possible to work through such disagree-
ments with time and sensitive communication.
In some such cases, the cited guidance allows for
DNACPR decisions not to be discussed with the
patient or their delegated decision-maker. This
applies to situations where the treating team have
strong reason to believe that such discussions will
cause significant distress or where the patient has
asked not to be involved in such discussions. Citing
risk of distress should not be undertaken lightly; any
such judgement should be carefully documented and
backed up with evidence – such decisions have been
challenged in court.
It is important to reinforce that the clarity of the deci-
sion is not a factor in considering whether to discuss a
DNACPR order. Even where CPR has no chance of
success, serious consideration should still be given to
discussion.
Unclear benefits/burdens: a person with capacity. A
competent patient can decline CPR and a DNACPR
document can be completed based solely on this deci-
sion, provided the clinician completing the document is
satisfied that the patient has capacity for the decision
and understands it.
Whilst a competent patient may decline CPR, they
may not insist on receiving CPR in the event that
they suffer a cardiac arrest, if it is deemed that CPR
would not succeed. Where there is a possibility of
success, eliciting and respecting the patient’s wish is
crucial. Such discussions should be handled sensitive-
ly, and the patient given the opportunity to consider the
discussion and invite family members/carers to
support them.
There are further subtleties to these decisions, but
such discussion is outside the remit of this work.
Examples include a patient refusing discussion, or a
patient delegating a decision to healthcare profes-
sionals. Current professional guidance is helpful in
working through these situations.9,10
Unclear benefits/burdens: a person with recent loss of
capacity. If the patient has recently lost capacity for
such decisions, some questions need to be asked:
• Have they previously discussed and agreed to a
DNACPR?
• Have they made some other form of advanced
decision to refuse treatment/living will?
• Have they been party to ‘Advance Care
Planning’?
• If so, are the circumstances those previously
envisaged?
It could then be seen as reasonable to let this inform
the current decision. It is also important to know
whether the patient, when competent, appointed
someone with lasting power of attorney under the
terms of the Mental Capacity Act, 2005 – in which
PALLIATIVE AND SUPPORTIVE CARE IN HEAD AND NECK CANCER: UK GUIDELINES
case this person should be approached, bearing in mind
that they, no more than the patient, can insist on treat-
ment, only decline it – see above.
Unclear benefits/burdens: a person with longstanding
loss of capacity. If the patient has a longstanding loss
of capacity, then the decision is left to the doctor(s)
and other members of the team to act in the patient’s
best interest, in accordance with the provisions of the
Mental Capacity Act. Where available, family, next of
kin and carers can be asked if they are aware of any opi-
nions expressed previously by the patient, etc. – again
noting that they cannot actually make the decision,
only inform the process. In situations where the patient
is alone then under the Mental Capacity Act one must
involve Independent Mental Capacity Advocate to con-
tribute to the decision- making process.
Further considerations
It is not possible to cover all eventualities for these
decisions, and professional guidance exists and
should be followed. Two further issues warrant discus-
sion, however; managing unresolved disagreements
and transfer to the home environment.
Despite the emotive nature of the subject and com-
plexity of decisions, it is usually possible to work
through DNACPR decisions to the agreement of the
patient, their loved ones and the clinical team. As
described above, a second opinion can be helpful in
resolving a disagreement. Occasionally no agreement
can be reached between doctor, the team, the patient
and those close to the patient. In extreme cases, particu-
larly where the patient lacks capacity, legal advice may
be required and consideration given to more formal
measures such as the involvement of the Court of
Protection.
A further point to highlight is the transfer of
DNACPR decisions to the home environment. In such
context, the patient and their family/carers are respon-
sible for the documentation and, as such, are able to
ignore or withhold it if they wish. For this reason,
clear communication and agreement in advance are vital.
Recommendations
• Cardiopulmonary resuscitation is
inappropriate in the palliative dying patient
(R)
• ‘Do not attempt cardiopulmonary
resuscitation’ orders should be completed and
discussed with the patient and/or the family
unless good reasons exist not to do so where
appropriate. This is absolutely necessary
when a patient’s care is to be managed at
home (G)
S207
Key points
• Palliative care takes an holistic approach addres-
sing physical,psychological, social and spiritual
needs of the patient,their carers and family
• Symptoms should be actively sought and treated
in a pro active manner by the multidisciplinary
team
• Pain is very common, affecting most patients at
some point and maybe disease or treatment
related.
• Constipation develops in half of patients who are
terminally ill with cancer admitted to hospice
• Confusion can affect up to 75% of cancer patients
at some stage.
• Spinal metastases should be considered where
there is new or progressive back pain and investi-
gated pro actively
• A key role of the doctor is to recognise when death
is imminent and should prompt a through review
of all care and interventions with unnecessary
medication being stopped.
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Address for correspondence:
Helen Cocks,
ENT Department,
City Hospitals Sunderland,
Sunderland
E-mail: helen.cocks@chfst.nhs.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S208–S211. GUIDELINE
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Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000645

Follow-up after treatment for head and neck

cancer: United Kingdom National Multidisciplinary
Guidelines

R SIMO1, J HOMER2, P CLARKE3, K MACKENZIE4, V PALERI5, P PRACY6, N ROLAND7

1
Department of Otolaryngology – Head and Neck Surgery, Guy’s and St Thomas’ Hospital NHS Foundation Trust,
Guy’s, King’s and St Thomas’ Medical and Dental School, London, 2Department of Otolaryngology – Head and
Neck Surgery, Manchester Royal Infirmary and Christie Hospital, University of Manchester, Manchester,
3
Department of ENT, Charing Cross and Royal Marsden Hospitals, London, 4Glasgow Royal Infirmary, University
of Glasgow, Glasgow, 6Department of ENT Head and Neck Surgery, Queen Elizabeth Hospital, Birmingham,
5
Department of Otolaryngology-Head and Neck Surgery, The Newcastle upon Tyne Hospitals NHS Foundation
Trust, Northern Institute of Cancer Research, Newcastle upon Tyne, and 7Department of Otolaryngology-Head and
Neck Surgery, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. In the absence of high-level evidence base for follow-up practices, the duration and
frequency are often at the discretion of local centres. By reviewing the existing literature and collating
experience from varying practices across the UK, this paper provides recommendations on the work up and
management of lateral skull base cancer based on the existing evidence base for this rare condition.
Recommendations
• Patients should be followed up to a minimum of five years with a prolonged follow-up for selected patients. (G)
• Patients should be followed up at least two monthly in the first two years and three to six monthly in the
subsequent years. (G)
• Patients should be seen in dedicated multidisciplinary head and neck oncology clinics. (G)
• Patients should be followed up by dedicated multidisciplinary clinical teams. (G)
• The multidisciplinary follow-up team should include clinical nurse specialists, speech and language therapists,
dietitians and other allied health professionals in the role of key workers. (G)
• Clinical assessment should include adequate clinical examination including fibre-optic rigid or flexible
nasopharyngolaryngoscopy. (R)
• Magnetic resonance imaging and positron emission tomography combined with computed tomography
imaging should be used when recurrence is suspected. (R)
• Narrow band imaging can be used in the follow-up in selected sites. (R)
• Second primary tumours should be part of rationale of follow-up and therefore adequate screening strategies
should be used to detect them. (G)
• Patients should be educated with regard to the appearance and detection of recurrences. (G)
• Patients with persistent pain should be investigated to exclude recurrent disease. (R)
• Patients should be offered support with tobacco and alcohol cessation services. (R)

Introduction • Early detection of new primary tumours

It is accepted that the follow-up of patients who had
treatment for head and neck cancers is a fundamental
part of their care.1–4 The reasons of post-treatment
follow-up include:
• Evaluation of treatment response
• Early identification of recurrence
• Monitoring and management of complications
• Optimisation of rehabilitation
• Provision of support to patients and their families.
Controversy exists in how these aims are achieved.5,6
Increasing efforts are being made to rationalise the struc-
ture and timing of head and neck follow-up clinics.
FOLLOW-UP AFTER TREATMENT FOR HEAD AND NECK CANCER: UK GUIDELINES
The general structure of follow-up clinics is to have
initial high-frequency visits especially in the first two
years when the risk of loco-regional recurrence is
known to be high and then reduce frequency, with
follow-up often finishing at five years. In the UK, the
structure of these clinics is often arbitrary and reflects
institutional and clinician-led practices with very little
evidence to support any one system.
Evidence to support follow-up for early detection of
tumour recurrence is lacking. However, there is a belief
that follow-up clinics have inherent value and to date
all published studies recognise this fact.7
In order to rationalise follow-up, patients could be
divided into low and high risk. This is well recog-
nised in thyroid cancer, but it is not the case in all
other types of head and neck cancer especially squa-
mous cell carcinoma (SCC). It is a belief that, this
categorisation could help to determine which patients
should be followed for more than five years. It would
also help to establish which screening test may be
needed in order to detect recurrence or second
primaries.
General considerations
Length
The length of follow-up is generally five years although
there are many clinicians who follow-up patients for
longer periods or even for life.8 Follow-up of patients
over five years would be justified for the following
groups: high-risk patients, specific tumours (e.g.
adenoid cystic carcinomas), patients who have under-
gone complex treatments who require on-going
rehabilitation and support, detection of new primary
tumours and patient preference. Fear of recurrence is
prevalent in cancer patients and continued attendance
at clinic helps to mitigate this.
Recommendation
• Patients should be followed up to a minimum
of five years with a prolonged follow-up for
selected patients (G)
Frequency
At present, there is no evidence that high frequency of
follow-up visits confers any benefit in terms of morbid-
ity and mortality. However, there is evidence that the
majority of clinicians in the UK support the follow-
up of patients, in regular high-frequency intervals in
the first two years when the risk of locoregional recur-
rence is high followed by a decrease in frequency after
the second year. The follow-up in the first two years
should be between four to eight weeks and from
three to six months thereafter.7
S209
Recommendation
• Patients should be followed up at least
two monthly in the first two years and
three to six monthly in the subsequent
years (G)
Setting
At present, 90 per cent of the clinicians treating
head and neck cancer in the UK see the patients in dedi-
cated head and neck clinics for the duration of the
follow-up.
Recommendation
• Patients should be seen in dedicated
multidisciplinary head and neck oncology
clinics (G)
Type of health professional
At present patients are followed up by their treating
clinicians and their teams. Allied health professionals
including speech and language therapists, dieticians
and clinical nurse specialists may offer specific
follow-up in their areas of expertise, but this is
usually in addition to the medical follow-up. The intro-
duction of the clinical nurse specialist and the key
worker role in the management of patients with head
and neck cancer has opened lines of communication
between the patient and family and the clinical team9
should any problems arise.
Recommendations
• Patients should be followed up by the
dedicated multidisciplinary clinical teams (G)
• The multidisciplinary follow-up team should
include clinical nurse specialists, speech and
language therapists, dietitians and other allied
health professionals in the role of key
workers (G)
Clinical assessment
Traditionally, clinical assessment has been the most
important aspect of the follow-up in patients treated
for head and neck cancer. The clinical evaluation is
done by inspection, palpation and at present with
fibre-optic rigid or flexible nasopharyngolaryngoscopy.
Rigid stroboscopy can also be used in patients who have
been treated for laryngeal cancer.
S210
Recommendation
• Clinical assessment should include adequate
clinical examination, including fibre-optic rigid
or flexible nasopharyngolaryngoscopy (R)
Screening investigations
Currently there is evidence that magnetic resonance
imaging (MRI) and positron emission tomography
combined with computed tomography (PET–CT)
scanning are superior at detecting recurrence and
second primaries.10,11 This is especially true in some
tumour sites such as the nasopharynx and following
treatment with chemo-radiation. Positron emission
tomography combined with computed tomography
has also the advantage of being a systemic evaluation.
Diffusion-weighted MR has been recently applied with
promising results; however, its accurate interpretation
requires specific training and experience. Narrow
band imaging12 (NBI), possibly associated with high
definition television technology, has been shown to
be an adjunctive imaging tool due to its specific cap-
ability to selectively address superficial persistences
and/or recurrences or second primary tumours by
enhancing their pathognomonic neoangiogenetic
pattern. It has been reported that its use can detect 18
per cent more true positive laryngeal cancerous
lesions than conventional white light endoscopy. This
is true even after radiotherapy (RT) or chemoradiother-
apy, due to the high accuracy (98 per cent) of NBI in
differentiating between neoplastic disease and post-
RT inflammatory and/or cicatricial changes.
Recommendations
• Magnetic resonance imaging and PET–CT
imaging should be used when recurrence is
suspected (R)
• Narrow band imaging can be used in the
follow-up in selected sites (R)
Second primary tumours
The incidence of second primary tumours varies
between 5 and 12 per cent at five years. There is
good evidence to indicate that patients with head
and neck SCC have an increased risk of developing
second primary malignant tumours.13,14 This risk
appears to be constant throughout the follow-up
period, with an incidence ranging from 2 to 4 per
cent per year. Traditionally, patients undergoing
follow-up for head and neck cancer underwent a
chest radiograph every year. However, there is
R SIMO, J HOMER, P CLARKE et al.
evidence that these have not been able to identify
metastasis with any confidence.
Recommendation
• Second primary tumours should be part of
rationale of follow-up and therefore adequate
screening strategies should be used to detect
them (G)
Specific considerations
Second-look microlaryngoscopy
In laryngeal cancer, especially in those patients treated
with transoral laser microsurgical excision, it is advis-
able to perform second-look microlaryngoscopy,15
especially in scenarios where there is lack of agreement
between the intraoperative and histological findings
regarding the completeness of resection. The rationale
of this is to provide evidence of complete resection,
detect residual tumour and to perform further treatment
should this be necessary.
Patients with persistent or recurrent pain without
clinical evidence of disease
Pain complaints must be regarded as a serious warning
sign of recurrent disease during follow-up of HNC
patients,16,17 even in the absence of an endoscopically
visible persistence and/or recurrence. Persistent neck
pain can be the first symptom of recurrent disease in
70 per cent of patients and can be an independent pre-
dictor of both recurrence and five-year survival rate.
Pain should always prompt the clinician to initiate a
thorough set of investigations, both by imaging and/
or endoscopy under general anaesthesia, in order to
reduce possible diagnostic delays. Pain without endo-
scopic evidence of disease is more frequently encoun-
tered after RT or chemoradiotherapy, but it is possible
even after surgery. This symptom is usually caused by
submucosal disease recurrence possibly hidden by
oedematous mucosa, or associated with chondritis,
chondronecrosis or osteonecrosis as a result of previ-
ous treatments.
Tumour markers
There is no evidence that the use of tumour markers is
any value in the follow-up of patients with head and
neck SCCs. The use of tumour markers in the follow-
up of patients with thyroid cancer is addressed else-
where in these guidelines.
Patient education
It has been recognised that the education of patients
plays an essential role in the detection of recurrences.
The vast majority of recurrences are diagnosed follow-
ing the occurrence of new symptoms and thus patients
should be educated about the need to seek help when
FOLLOW-UP AFTER TREATMENT FOR HEAD AND NECK CANCER: UK GUIDELINES
appropriate. It has also been recognised that continuing
smoking and alcohol drinking increases the risk of
recurrence and second primary tumours. It is therefore
imperative that patients are advised and offered support
with regards to the detrimental effects of tobacco
smoking and alcohol addiction.
Recommendations
• Patients should be educated with regards to the
appearance and detection of recurrences (G)
• Patients with persistent pain should
investigate to exclude recurrent disease (R)
• Patients should be offered support with
tobacco and alcohol cessation services (R)
Key points
• The aims of follow up of patients after treatment
for head and neck cancers are manifold
• The frequency of follow-up is higher in the first
two years, with reduced frequency subsequently,
finishing at five years
• Medical, nursing and allied health professionals
all play important roles in providing follow up care
• Change in patient symptoms during follow up is
the most frequent indication of recurrent disease
and must be regarded seriously, even if clinical
examination reveals no abnormalities.
References
1 Simo R, Bradley P, Chevalier D, Dikkers F, Eckel H, Matar N,
et al. European Laryngological Society. ELS Recommendations
for the follow-up of patients treated for laryngeal cancer. Eur
Arch Otorhinolaryngol 2014;27:2469–79
2 Joshi A, Calman F, O’Connell M, Jeannon JP, Pracy P, Simo R.
Current trends in the follow-up of Head and Neck Cancer
patients in the UK. Clin Oncol 2010;22:114–8
3 Kothari P, Trinidade A, Hewitt RJD, Singh A, O’Flynn P. The
follow-up of patients with head and neck cancer: an analysis
of 1039 patients. Eur Arch Otorhinolaryngol 2011;268:
1191–200
4 Digonnet A, Hamoir M, Andry G, Haigenz M, Takes RP,
Vander Poorten V et al. Post-therapeutic surveillance strategies
S211
in head and neck squamous cell carcinoma. Eur Arch
Otorhinolaryngol 2013;270:1569–80
5 Haas I, Houser U, Gancer U. The dilemma of follow-up in head
and neck cancer. Eur Arch Otorhinolaryngol 2001;258:177–83
6 Morton R, Hay KD, Macann A. On completion of curative treat-
ment of head and neck cancer: why follow-up? Curr Opin
Otolaryngol Head Neck Surg 2004;12:142–6
7 National Institute of Care Excellence (NICE). Improving
Outcomes in Head and Neck Cancers – The Manual. 2004
http://www.nice.org.uk/guidance/CSGHN (accessed 20
October 2015)
8 Schwartz DL, Barker J Jr, Chansky K, Yueh B, Raminfar L,
Drago P, et al. Postradiotherapy surveillance practice for head
and neck squamous cell carcinoma – too much for too little?
Head Neck 2003;25:990–9
9 Trinidade A, Kothari P, Andreou Z, Hewitt RJ, O’Flynn P.
Follow-up in head and neck cancer: patient’s perspective. Int J
Health Care Qual Assur 2012;25:145–9
10 Ul-Hassan F, Simo R, Guerrero-Urbano T, Oakley R, Jeannon
JP, Cook GJ. Can (18)F-FDG PET/CT reliably assess response
to primary treatment of head and neck cancer? Clin Nucl Med
2013;38:263–5
11 Isles MG, McConkey C, Mehanna HM. A systematic review and
meta-analysis of the role of positron emission tomography in the
follow-up of head and neck squamous cell carcinoma following
radiotherapy or chemoradiotherapy. Clin Otolaryngol 2008;33:
210–22
12 Piazza C, Cocco D, De Benedetto L, Del Bon F, Nicolai P,
Peretti G. Narrow band imaging and high definition television
in the assessment of laryngeal cancer: a prospective study on
279 patients. Eur Arch Otorhinolaryngol 2010;267:409–14
13 Leon X, Quer M, Diez S, Orus C, Lopez-Pousa A, Burgues J.
Second neoplasm in patients with head and neck cancer. Head
and Neck 1999;21:204–9
14 Leon X, Martinez V, Lopez M, Garcia J, Quer M. Risk of third
and fourth tumours in patients with head and neck cancer. Head
and Neck 2010;32:1467–72
15 Preuss SF, Cramer K, Drebber U, Klussman JP, Eckel HE,
Gunitinas-Lichius O. Second-look microlaryngoscopy to
detect residual carcinoma in patients after laser surgery for T1
and T2 laryngeal cancer. Acta Otolaryngol 2008;16:1–5
16 Bradley PJ, Mackenzie K, Wight R, Pracy P, Paleri V.
Consensus statement on management in the UK: transoral
laser assisted microsurgical resection of early glottic cancer.
Clin Otolaryngol 2009;34:367–73
17 Scharpf J, Karnell LH, Christensen AJ, Funk GF. The role of
pain in head and neck cancer recurrence and survivorship.
Arch Otolaryngol Head Neck Surg 2009;135:789–94
Address for correspondence:
Ricard Simo,
Department of Otolaryngology – Head and Neck Surgery,
Guy’s and St Thomas’ Hospital NHS Foundation Trust,
Guy’s, King’s and St Thomas’ Medical and Dental School,
London, UK
E-mail: ricardsimo1@icloud.com
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S212–S215. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000657

The clinical nurse specialist’s role in head and neck

cancer care: United Kingdom National
Multidisciplinary Guidelines

L DEMPSEY1, S ORR2, S LANE1, A SCOTT3

1
Aintree University Hospitals NHS Foundation Trust, Liverpool, 2University College Hospitals London (UCLH),
British Association of Head and Neck Oncology Nurses, and 3East & North Hertfordshire NHS Trust, British
Association of Head and Neck Oncology Nurses, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. It discusses the role of the clinical nurse specialist in the head and neck cancer patient
journey and provides recommendations on the clinical nurse specialist led assessments and interventions for this
group of patients receiving cancer care.

Recommendations
• All cancer patients should meet a clinical nurse specialist at the point of diagnosis. (R)
• Clinical nurse specialists must act as gate keeper to the patients’ cancer pathway to provide a seamless
journey. (R)
• Holistic needs assessment should be completed at different stages of the patient’s pathway to reflect the changes
of the patients’ needs. (R)
• Clinical nurse specialists to be part of local and national initiatives for health promotion and raising awareness
in the public domain. (G)
• Clinical nurse specialists should lead in redesigning of services and policies to ensure they are responsive to
patient’s needs for the future. (G)
• Treatment summaries should become part of practice to provide good communication between primary and
secondary care to enable continuity of care for the patient. (G)

Introduction cases, role reversal within the family unit. Patients

Distress is common among cancer patients; it is multi-
factorial, comprising of psychological, social and spir-
itual elements which can impact on an individual’s
ability to cope effectively with cancer. A diagnosis of
cancer leaves patients frightened and vulnerable,
often unable to understand the full implication of the
treatment they are being offered.1 It can, in extreme
cases, impact on the ability to adhere to treatment and
self-management. It is widely recognised that head
and neck cancer patients are particularly vulnerable to
psychological distress as many suffer life-changing,
long-term consequences resulting from the cancer and
the treatment.2,3
Carers of patients with head and neck cancer are
under considerable stress during and after treatment
as a result of disruption to daily life, the financial and
emotional strain of long-term treatment and in many
and carers look to healthcare professionals to provide
information to help manage the psychological and
social elements of head and neck cancer.4 Supportive
care, appropriate information and individualised care
planning is a key to improve the experience of the
patient and the carer.
It is the function of the clinical nurse specialist
(CNS) to give the patient and carer the wherewithal
to cope with the diagnosis, treatment and long-term
consequences through the use of empathy and
experience.5–8 The Cancer Reform Strategy9 recog-
nises that the CNS is critical in the delivery of infor-
mation, communication and co-ordination of care. It
has been recognised that care co-ordination indivi-
dualised to the patient during and after treatment is
vital to deliver appropriate person-centred care.10
The CNS’ role within the multidisciplinary team
CLINICAL NURSE SPECIALIST IN HEAD AND NECK CANCER CARE: UK GUIDELINES
(MDT) also allows for easy and timely referral on to
other resources, i.e. palliative care and psychological
support.
The role of the clinical nurse specialist
(figure 1)
The National Institute for Health and Care Excellence
Improving Outcomes Guidance11 identified the key
worker as ‘A person who with the patient’s consent
and agreement takes a key role in co-ordinating the
patient’s care and promoting continuity, ensuring the
patient knows who to access for information and
advice’. The CNS will act as the patient’s key worker
during their cancer pathway by providing specialist
cancer knowledge and expertise to both the patient
and carer, which can be both complex and disjointed,
involving interventions from multiple professionals or
agencies.6 The CNS reinforces and imparts their spe-
cialist knowledge to the other professionals and agen-
cies to improve the cancer process and in turn will
improve the cancer journey for the patient and carer.
The CNS may pass the key worker role on to another
relevant professional when the patient is on a particular
part of the pathway, as this may be in their best interests
and provide the best support at that particular point of
their journey.
The CNS workload can be complex and varied
dependent on the patient’s needs, it can be categorised
into themes:
• Specialist technical knowledge of the cancer
process and treatment options
FIG. 1
Key contributions of the clinical nurse specialist to cancer care.
S213
• Acting as the patient’s key worker for a specific
part of the process and linking in with the MDT
• Utilising advanced communication skills to
support the patient and carer psychologically
through the disease process
• Lead on redesigning services to make them
responsive to the patient’s needs
• Health education and promotion to reduce the risk
of recurrence and promote a healthy lifestyle
• Assisting in local and national initiatives to
promote awareness and prevention.
The role of the CNS within the MDT
The CNS acts as the key accessible professional to the
patient within this multiprofessional setting, and allows
the CNS to influence the patient’s pathway. They are
well placed to support the patient at each stage of
their pathway and promote integration within the
team. The CNS should be recognised as the patient’s
advocate within the MDT meetings where they
deliver patient-centred care tailored to the individual
patient’s needs. In acting as the patients’ advocate,
the CNS also plays a key role in ensuring that the multi-
disciplinary care is responsive to the patients’ needs
and preferences.12
The CNS and the patient’s pathway
Clinical nurse specialists increasingly take the lead role
in shaping patient care pathways and refining systems
to make a difference to the patient experience and
their safety. By acting as the key worker,13 they
provide information, support and liaison to improve
S214
the cancer care process for the patient. They can track
the stage of their pathway and ensure it is seamless
and prevent any problems from occurring. They are
well placed with in the organisation to assist in
system changes to ensure the pathway represents a
quality service that fulfils the standards of cancer care
and patients’ expectations.
The patient’s role as advocate
Patients and carers have always been at the centre of
cancer services, but have not always been encouraged
or empowered to help influence and shape them.14
Patient support groups have traditionally played a
large part in providing information, companionship
and peer support for patients and carers throughout
their cancer journey. They can also influence policy
and services at local, national and at international
level.
The Cancer Plan15 saw the patient involvement
being embedded in cancer services. This involvement
has continued with organisations like National
Cancer Research Institute (NCRI) having representa-
tion on all its clinical study groups and funding com-
mittees. This is also happening on cancer strategy
committees and clinical network groups.
Patients and carers now have a realisation that they
have considerable influence in gaining access to treat-
ments and medicines, can participate in the designing
of clinical trials and influence the amount of money
spent by central government on research.14 It is import-
ant to understand that patients provide a very different
perspective on benefits vs risks of treatment.16 They
will very often opt for extensive and often life threaten-
ing treatment even if the benefits and outcomes are
unclear.
Managing patients’ and carers’ expectations
A diagnosis of cancer has far reaching effects beyond
the patient to their loved ones. This life-changing
experience means that relationships and roles and
responsibilities can often be changed. Treatments for
head and neck cancer can have devastating effects on
the lives of patients, including disfiguration, speech
and swallowing impairment.17
‘The Recovery Package’18 has been designed by
Macmillan Cancer Support to help ‘provide a series
of key interventions, which when delivered together
can greatly improve outcomes for people living with
and beyond cancer’. It is made up of:
• Holistic needs assessment
• Treatment summary
• Cancer care review
• Education and support events.
It also compliments stratified care plans, which enable
individualised follow-up care and self-support. It facili-
tates urgent access back to the specialist team if needed
or on-going support from healthcare professionals.
L DEMPSEY, S ORR, S LANE et al.
Recommendations
• All cancer patients should meet a cinical nurse
specialist at the point of diagnosis (R)
• Clinical nurse specialists must act as gate
keeper to the patient’s cancer pathway to
provide a seamless journey (R)
• Holistic needs assessment (HNA) should be
completed at different stages of the patient’s
pathway to reflect the changes of the patients’
needs (R)
• Clinical nurse specialists to be part of local
and national initiatives for health promotion
and raising awareness in the public domain
(G)
• Clinical nurse specialists should lead in
redesigning of services and policies to ensure
they are responsive to patient’s needs for the
future (G)
• Treatment summaries should become part of
practice to provide good communication
between primary and secondary care to
enable continuity of care for the patient (G)
Holistic needs assessment
An HNA ensures that the patients’ and carers’ physical,
emotional and social needs are met in a timely and
appropriate way, and that advice and support is avail-
able from the right source at the right time.19 The
HNA is the process of assessing the patient and/or
carers by developing an understanding of what the
person with cancer understands and needs at diagnosis
and various time points thereafter which can be agreed
by the MDT or when clinically appropriate (i.e. disease
progression). This discussion may cover all or some of
the following areas – physical, spiritual, emotional,
social and environmental needs. Undertaking holistic
needs assessment with a patient enables them to more
fully engage in their own care and make informed
choices. The information gathered at the HNA can
also be shared with other members of the MDT and
also have influence on service needs and data collec-
tion. The National Cancer Survivorship Initiative
(NCSI) in 2010 highlights HNA as one of its ‘Key
Shifts’ as well as it being a Peer Review Measure.
Different assessment tools are used, i.e. distress
thermometer, concerns checklist and more recently
the patient concerns inventory. The tools can be used
at different stages along the patient trajectory, but
with an emphasis being on assessing and eliciting
patients’ and carers’ concerns and expectations. This
leads to a discussion and care planning of the patients’
needs and helps to manage expectations.
Pre-treatment clinics provide an opportunity for
patients and carers to meet the CNS and other allied
CLINICAL NURSE SPECIALIST IN HEAD AND NECK CANCER CARE: UK GUIDELINES
health professionals prior to surgical or oncological
treatment. It allows HNA assessment to take place,
but also facilitates discussion of acute treatment and
rehabilitation with the key professionals involved
prior to commencement of such.
Care plans
A care plan is based on the diagnosis and holistic
assessment of the patient.19 It will highlight the
patient’s issues, outlining any actions, approaches and
timings to address them. Care plans change during
the patient pathway according to the patient’s needs
at any one time; however, any change should be dis-
cussed and actions agreed with the patient. By
working with the patient to develop care plans follow-
ing an HNA, the patient is able to take more control
of what happens to them and support themselves to
self-manage their condition.20
Treatment summary
A key component to effective patient care is good com-
munication between the primary and secondary care
sectors. Making sure that general practitioners are
fully informed about their patients’ cancer journeys
can ease the transition between acute and long-term
care. For this to be effective, treatment summaries are
provided at the end of any acute treatment by the
MDT for the general practitioner and patient. The treat-
ment summary describes the treatment that that person
has received, including any adverse reactions, the side
effects and signs and symptoms of recurrence. This
treatment summary provides confidence to the patient
that their care is continuing albeit in the community
setting. Patients report feelings of abandonment and
vulnerability once initial treatment is complete but
with a treatment summary and care plan these feelings
can be minimised. Patients’ on-going self-management
can be well supported through peer support groups and
health and wellbeing events. The CNS is obliged to
inform patients of what is available in the local area
that may be accessed by the patient and carer.
Key points
Clinical nurse specialists should:
• meet every patient at the point of diagnosis to
assist in a smooth transition along the cancer
pathway
• ensure effective communication within the MDT,
with patient and carer and within the community
setting
• be at the centre of the patient’s pathway and make
effective use of resources
• act as the patient advocate, utilising support
groups to act as patient voices in the changing
healthcare environment to make them patient-
centred
• perform holistic needs assessment for all patients
at diagnosis and specific points along their
S215
journey to ensure patient-focused care is being
provided
• offer treatment summaries to all people involved
in the patient’s recovery to ensure effective
communication
• offer individualised care plans to help patients take
control of the recovery phase.
References
1 We are Macmillan Cancer Support. Worried Sick: The
Emotional Impact of Cancer, 2007:1–28
2 Ghazi N, Kantas A, Bekiroglu F, Scott B, Lowe D, Rogers SN.
The patient’s concerns inventory: a tool to uncover unmet needs
in a cancer outpatient clinic. Ann R Coll Surg Engl (Suppl) 2013;
95:1–6
3 Humphris G. Psychological management for head and neck
cancer patients: United Kingdom National Multidisciplinary
Guidelines. J Laryngol Otol 2016;130(Suppl S2):S45–8
4 Zhou Y, Humphris G, Ghazali N, Friderichs S, Grosset D, Rogers
SN. How head and neck consultants manage patients’ emotional
distress during cancer follow-up consultations: a multilevel study.
Eur Arch Otorhinolaryngol 2015;272:2473–81
5 We Are Macmillan Cancer Support: Cancer Clinical Nurse
Specialist: Impact Briefs, 2011:1–14
6 National Cancer Action Team. Quality in Nursing: Excellence in
Cancer Care: The Contribution of the Clinical Nurse Specialist
London, 2010:1–16
7 Department of Health, We are Macmillan Cancer Support &
NHS Improvement. Living with and beyond cancer: taking
actions to improve outcomes, March 2013:1–135
8 Ghazali N, Cadwallader E, Lowe D, Humphris G, Ozakinci G,
Rogers SN. Fear of recurrence among head and neck cancer sur-
vivors: longitudinal trends. Psychooncology 2013;22:807–13
9 Department of Health. Cancer reform Strategy London, 2007:1–44
10 de Leeuw J, Prins JB, Uitterhoeve R, Merkx MA, Marres HA,
van Achterberg T. Nurse-patient communication in follow-up
consultations after head and neck cancer treatment. Cancer
Nurs 2014;37:E1–9
11 National Institute for Care Excellence. Improving Outcomes in
Head and Neck Cancers, November 2004:43–4
12 Leary A, Oliver S. Clinical nurse specialists: adding value to
care RN Forum, Ed. Royal College of Nursing, London, April
2010:1–8
13 Psychology Support Working Group. Key Worker Guidelines.
Cheshire & Merseyside Strategic Clinical Network, October
2009:1–12
14 Fricker J. Patient advocacy groups: empowering patients in their
fight against cancer. Mol Oncol 2007;1:252–4
15 Department of Health. The NHS Cancer Plan. A plan for invest-
ment, A plan for reform. 2000. http://webarchive.nationalarchives.
gov.uk/+/www.dh.gov.uk/en/Publicationsandstatistics/Publications/
PublicationsPolicyandGuidance/DH_4009609 (accessed 27 April
2016)
16 Birchall M, Richardson A, Lee L. Eliciting views of patients
with head and neck cancer and carers on professionally
derived standards for care. BMJ 2002;324:516
17 We are Macmillan Cancer Support. Cured but at what cost?
Long-term consequences of cancer and its treatment, 2013:1–28
18 Rowe J, Young N, Rowlands S. The Recovery Package. We are
Macmillan Cancer Support, Spring 2014:1–20
19 Young N, Smith LSA, Wilkinson A. Holistic needs assessment
and care planning. We are Macmillan Cancer Support, Winter
2012:1–16
20 Department of Health, We are Macmillan Cancer Support &
NHS Improvement. Stratified pathways of care for people
living with or beyond cancer: A “how to guide”, 2013:1–103
Address for correspondence:
Lesley Dempsey,
Aintree University Hospitals NHS Foundation Trust,
Liverpool, UK
E-mail: lesley.dempsey@aintree.nhs.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S216–S217. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000669

Clinical research, national studies and

grant applications: United Kingdom National
Multidisciplinary Guidelines

N STAFFORD

Department of Otolaryngology-Head and Neck Surgery, University of Hull, Hull and East Yorkshire Hospitals NHS
Trust, Hull, UK

Abstract
Head and neck cancer clinical research is thriving. Infrastructure for clinical research is supported through the
National Institute for Health Research Clinical Research Network with operates through 15 local clinical
research networks for studies within the UK Clinical Research Network Portfolio. The National Clinical
Research Institute is a partnership of UK cancer research funders that support high-quality cancer research,
although the National Institute for Health Research also has funding streams that will fund cancer-related
research. Their websites provide up-to-date information regarding ongoing research projects. Other specialty
organisations such as the British Association of Head and Neck Oncologists play important subsidiary roles in
supporting research.

Clinical research into head and neck cancer is an active
and increasing area of activity in the UK. Several active
research centres where clinical trials are underway are
distributed evenly through the UK. The framework
for the organisation and infrastructure support of clinic-
al cancer research is supported through the National
Institute for Health Research (NIHR) Clinical
Research Network (CRN). The NIHR CRN is the clin-
ical research delivery arm of the National Health
Service (NHS) in England, tasked with supporting
the rapid set up and effective conduct of studies in
the UK Clinical Research Network Portfolio, so that
researchers can gather the robust evidence needed to
improve treatments for NHS patients. The CRN oper-
ates across the NHS through a national coordinating
centre and comprises 15 local clinical research net-
works (LCRNs) that cover the length and breadth of
England. Each LCRN delivers research across 30 clin-
ical specialties. At a local level the LCRN is respon-
sible for the provision and allocation of research
infrastructure including research nurses in collaboration
with each partner organisation – each NHS Trust. The
clinical specialties within each LCRN are managed
across six divisions. Clinical research in head and
neck cancer falls under ‘division 1’ – Oncology.
The National Cancer Research Institute (NCRI) is a
partnership of UK cancer research funders, govern-
ment, charity and industry. In addition to the NCRI,
the NIHR has several funding streams that support
cancer trials. The NCRI comprises both clinical and
managerial leadership. For each tumour type there are
clinical studies groups (CSGs) and there are also
modality CSGs, which cross cut the tumour site specif-
ic groups (e.g. radiotherapy CSG). The head and neck
CSG is a group of approximately 20 individuals. All
the specialties related to clinical cancer research are
represented – e.g. surgical specialties of head and
neck surgery (otolaryngology and maxillofacial
surgery), clinical and medical oncology, oral medicine,
head and neck pathology, radiology, clinical trials and
statistics, consumer representatives and administrative
support. The head and neck CSG is also attended by
representatives of the NCRI infrastructure as well as
the main funders – Cancer Research UK. Over the
last two years, the CGG has invited trainee representa-
tives from the relevant specialties to attend meetings for
a year, with the clear aim of growing tomorrow’s
research leaders. The membership of the CSG rotates
regularly and advertisements for positions on the
group are advertised both on the NCRI website as
well as in the national press. The current chairman is
Professor Hisham Mehanna at the University of
Birmingham.
A broad range of national studies is currently open,
including trials of surgery, radiation, chemotherapy
and other topics. For an up-to-date list of the current
CLINICAL RESEARCH, NATIONAL STUDIES AND GRANT APPLICATIONS
research protocols please consult the head and neck
section of the NCRI website (http://www.ncri.org.uk)
or search cancer ‘head and neck’ on the UK Clinical
Trials Gateway: https://www.ukctg.nihr.ac.uk/
For individuals interested in developing clinical
research several sources of help are currently available.
The CSG members function as ‘ambassadors’ who can
be approached for advice regarding the research idea.
Research design services, funded by the NIHR, are dis-
tributed across CRNs to develop the idea and write a
robust grant application, and also provide advice on
the available and appropriate funding streams. For
large randomised phase III trials, the two main
funders at the present time are Cancer Research UK
through the Clinical Trials Advisory and Awards
Committee and also the health technology assessment
(HTA) stream of the NIHR.
For feasibility studies Cancer Research UK remains
the main funder and they also support translational
research in relation to clinical trials. It is important to
engage with a pathologist during the development of
studies that might involve collecting and storing
human tissue and to be aware of the requirements of
the Human Tissue Authority. The role of pathology in
research is addressed on the NCRI website and the
MRC Data and Tissues Tool kit is being developed as
a signpost to good guidance (http://www.mrc.ac.uk).
S217
A number of other funding streams are available
including those coming direct from the department of
Health who put out regular calls for research proposals
via the NIHR. For smaller research projects in single
centres or pump priming grants the Royal College of
Radiologists and the British Association of Head and
Neck Oncologists are sources of potential funding.
Both of the above and also the Royal College of
Surgeons are sources of short-term research grants for
individuals. Useful web addresses for individuals
looking for research funding are given below.
http://www.cancerresearchuk.org/
http://csg.ncri.org.uk/
http://www.rcr.ac.uk
http://www.rcseng.ac.uk
http://www.bahno.org.uk
http://www.hta.ac.uk
http://www.nihr.ac.uk/funding-opportunities/
http://www.nihr.ac.uk/funding/funding-for-research.htm
Address for correspondence:
Nick Stafford,
Department of Otolaryngology-Head and Neck Surgery,
University of Hull,
Hull and East Yorkshire Hospitals NHS Trust,
Hull, UK
E-mail: n.d.stafford@hull.ac.uk
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S218–S221. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000670

Education of trainees, training and fellowships for

head and neck oncologic and surgical training in
the UK: United Kingdom National Multidisciplinary
Guidelines

R SIMO1, A ROBSON2, B WOODWARDS3, P NIBLOCK4, P MATTEUCCI5

1
Department of Otolaryngology – Head and Neck Surgery, Guy’s and St Thomas’ Hospital NHS Foundation Trust,
Guy’s, King’s and St Thomas’ Medical and Dental School, London, 2North Cumbria University Hospitals NHS
Trust, Cumberland Infirmary, Carlisle, 3Oral and Maxillofacial Unit, North Manchester General Hospital,
Manchester, 4Ninewells Hospital, Dundee, and 5Hull and East Yorkshire Hospitals NHS Trust, Hull, UK

Abstract
Since the previous edition of these guidelines, significant changes have taken place in the training and assessment of
surgeons and oncologists who treat patients with head and neck cancer. For those intending to become head and
neck surgeons, a fellowship in head and neck surgery is virtually mandatory. This paper summarises the current
career structure to specialise in head and neck oncology and surgery in the UK.
Recommendation
• Trainees applying for head and neck surgical oncology consultant posts should have completed additional training
in the subspecialty.

Introduction A curriculum consists of an aim, a syllabus, an

Education in the practice of head and neck oncology
(HNO) has been identified as one of the key challenges
in the management of head and neck cancer in the 21st
century. The re-structuring and shortening of the train-
ing programmes over the last two decades has pro-
moted the creation of interface and post-specialty
training dedicated fellowship posts, with the ultimate
aim of improving patient care. These changes
however, require a much more substantial input from
trainers which ultimately impacts on patient care, but
there is no doubt that better structured and dedicated
time in subspecialty training is required.
Educational principles
Training in head and neck surgical oncology (HNSO)
in the UK, both in the parent specialty and for interface
trainees are governed by a curriculum approved by the
General Medical Council. From 2007, all surgical trai-
nees have been required to follow the curriculum for
training as set out in the Intercollegiate Surgical
Curriculum project.1 Clinical oncology and medical
oncology training programmes are supervised by the
Royal College of Radiologists (RCR)2 and the Royal
College of Physicians (RCP)3, respectively.
assessment matrix and a process for evaluation. As
far as possible, trainees should be responsible for
their own learning and achieve the objectives set out
in the curriculum; trainers and overseeing bodies
such as deaneries and the specialist advisory commit-
tees (SAC) should facilitate the process by ensuring
that standards are met and that opportunities are
available.
At the beginning of a rotation, trainees should self-
assess their learning needs by comparing their current
level of knowledge or technical competence against
what is expected of them for their stage of training as
per the curriculum. Objectives are available within
the syllabus on the Intercollegiate Surgical
Curriculum Programme (ISCP). This will identify the
gap between what they know or can do compared
with what they need to know or achieve for technical
competence (a learning need). From this, a learning
plan or agreement can be agreed. This plan needs to
be constructed using SMART objectives (Specific,
Measurable, Achievable, Relevant and Timely) so
that, at the end of an attachment or programme, the
trainee can be assessed to ensure that objectives have
been achieved. The learning plan should be recorded
in the trainee’s portfolio.
EDUCATION OF TRAINEES, TRAINING AND FELLOWSHIPS: UK GUIDELINES
Assessment
Assessment is formative or summative. Summative
assessment usually takes the form of an examination
(FRCS, FRCR), is high stakes (pass or fail) and
usually occurs at the end of a programme or at
crucial waypoints along a programme (e.g. Member
of the Royal College of Surgeons (MRCS)).
Formative assessment should be viewed as an assess-
ment for learning, to identify strengths and weaknesses
in a trainee’s work and to highlight areas for develop-
ment. Formative assessment tools usually take the
form of workplace based assessments (WPBAs).
These are designed to assess the essential domains of
learning of knowledge, skills, professionalism and atti-
tudes and should be viewed as developmental rather
than punitive assessments.
An integral part of adult learning is the timely and
regular provision of constructive feedback. This has
to be used correctly to ensure it is viewed in a positive
manner. Feedback should be timely, relevant and con-
structive, usually given to best effect in private imme-
diately after a learning event. Provision of written and
verbal feedback is an integral part of WPBAs and
aids in the agreement of areas for development.
Each trainee will be awarded an Annual Record of
Competency Progression certificate (ARCP). This is
to ensure that there is documentary evidence to
confirm that the trainee has met his or her targets for
the year and is progressing satisfactorily. Annual
Record of Competency Progression certificate panels
are required to examine evidence of competence and
increasingly this is being carried out with more struc-
ture and objectivity than was the case with the
Record of In Training Assessment system. It is thus
imperative that evidence to support acquisition of com-
petency is recorded. An ARCP panel may recommend
specific targets that need to be attained (ARCP 2) or an
extension to training time if a trainee requires more
time to progress safely (ARCP 3).
Trainees with specific needs (Trainees with
Differing Needs) require skill, sensitivity and dedicated
time to ensure specific personal targets for training can
be agreed and met. Trainers and trainees should seek
and receive support from their deanery, employing
trust and SAC to ensure satisfactory progression.
Career structure in otorhinolaryngology,
head and neck surgery
Training in otorhinolaryngology, head and neck surgery
(ORL-NHS) starts as part of core surgical training
(CST) for two years. Entry to ST3 is by competitive
interview against personal specification including suc-
cessful acquisition of the Member of the Royal
Colleges of Surgeons (MRCS) (ENT).
Higher surgical training lasts six years and during
this time all trainees are expected to develop compe-
tence in all aspects of the specialty. Trainees should
take their Intercollegiate Exam from ST6 onwards. In
S219
the final two years trainees should spend more time
in their area of special interest including advanced fel-
lowship training. The SAC must prospectively approve
these posts for training.
Career structure in oral and maxillofacial
surgery
Oral and maxillofacial surgery (OMFS) is based on the
practitioner having both medical and dental degrees.
They must be on the specialist list in OMFS and be on
the General Medical Council (GMC) register.
Registration with the General Dental Council (GDC) is
optional, but in order to train the dental graduates one
must also be fully registered with the GDC.
Trainees traditionally have mostly followed the route
of dentistry first then medicine though, increasingly
medical graduates are following a path through a
second degree in dentistry to train in OMFS.
Once the dual degree is obtained, those who studied
medicine second, proceed through foundation training
(often only one year) into CST and Member of
the Royal College of Surgeons (MRCS). Once the
MRCS is obtained they are eligible to apply for a
post in specialty training in OMFS. Trainees with den-
tistry as a second degree need to decide if they are
likely to practise dentistry outside of OMFS, in which
case they will do dental foundation training for one to
two years; once the MRCS is acquired, they can
apply to a specialty training post in OMFS.
Specialty training in OMFS lasts five years. Trainees
may opt to take additional training in one of the Interface
Specialty Fellowships including HNSO, cleft lip and
palate, and cosmetic and reconstructive surgery.
Career structure in plastic surgery
The training programme, designed to last an indicative
eight years, includes training in areas of special interest.
It comprises three stages: initial (CT1 and 2), inter-
mediate (ST3–6) and final (ST7 and 8). Entry to ST3
is through a national recruitment process including a
competitive interview against personal specification
including successful acquisition of the intercollegiate
MRCS (there is no specific plastic surgical Member
of the Royal Colleges of Surgeons (MRCS) as there
is for ENT). The training is six years and during this
time all trainees will be expected to develop compe-
tence in all aspects of the specialty. Having completed
the syllabus, attained the required levels of competence
and passed the Intercollegiate Examination (usually
taken from ST6 onwards), the candidate will be eligible
to be awarded a Certificate of Completion of Training
(CCT).
Increasingly, at the end of training (ST7 and 8)
senior trainees are undertaking special interest fellow-
ships (see below), which take between 12 and 24
months to complete and are appointed through adver-
tisement and selection. These will usually result in
the deferment of the CCT until this is completed.
S220
Subspecialty fellowship options include: head and
neck surgery, aesthetic surgery, burns, ear reconstruc-
tion, genitourinary reconstruction, hand surgery, cleft
lip and palate, craniofacial, lower limb, oncoplastic
breast surgery (in combination with breast surgeons)
and skin oncology.
Career structure in oncology
Currently, in the UK, there are two main types of
oncologists concerned with the management of
patients with cancer: medical oncologists (MOs) and
clinical oncologists (COs). Both see and assess patients
with cancer and both specialities are part of the core
membership of cancer multidisciplinary teams
(MDTs).
Medical oncologists are physicians trained in the use
of systemic drug therapies for cancer, either alone or in
combination with other treatments. The RCP super-
vises training for MOs. Completion of both foundation
and core training programmes, culminating in full
MRCP, is required prior to entry into MO training.
Entry is at the ST3 level with a four-year specialist train-
ing programme leading, after passing the Specialty
Certificate Examination (SCE), to a Certificate of
Completion of Training in Medical Oncology.
Clinical Oncologists are trained in both systemic
drug therapy and in the use of radiotherapy.
Specialist training in CO also demands full MRCP
for entry and begins at the ST3 level. Training
takes five years and is supervised by the Royal
College of Radiologists (RCR). There is a two-part
examination leading to Fellowship of the RCR
(FRCR): Part 1, usually passed by the end of ST4,
covers the basic sciences of oncology and radiother-
apy, whereas Part 2, usually passed during the
fourth year of specialist training (ST6), is a clinically
based exam and covers the practical aspects of asses-
sing patients and delivering radiotherapy and systemic
drug therapy. The award of CCT is, for UK trainees,
dependent upon passing both parts of the FRCR
examination and completing a further minimum
period of one year to achieve advanced oncology
training and competencies.
Integrated and advanced fellowships
The Joint Committee on Surgical Training is an advis-
ory body to the four surgical Royal Colleges of the UK
and Ireland for all matters related to surgical training
and works closely with the surgical specialty associa-
tions in Great Britain and Ireland.
Although HNSO is yet to become a recognised spe-
cialty, the Joint Committee on Surgical Training and
the Specialty Advisory Committees in OMFS, ORL-
HNS and PS, through the Training Interface Group
(TIG),4 jointly have accredited and recognise several
national advanced head and neck surgery posts for
training. These fellowships are open to trainees in the
three specialties who are in a recognised training post
and have completed successfully their Intercollegiate
R SIMO, A ROBSON, B WOODWARDS et al.
Examination. The recognised fellowships are shown
in BOX I.
BOX I
TRAINING INTERFACE GROUP ACCREDITED HEAD
AND NECK SURGICAL ONCOLOGY FELLOWSHIP
PLACEMENTS
• Northern – Newcastle Hospitals NHS
Foundation Trust
• Northwest 1 – Central Manchester University
Hospitals NHS Foundation Trust
• Northwest 2 – Pennine Acute Hospitals NHS
Trust
• Oxford – Oxford University Hospitals NHS
Trust
• West Midlands – University Hospital
Birmingham NHS Foundation Trust
• West of Scotland – Glasgow Royal Infirmary and
Southern General Hospital
• Yorkshire – Hull and East Yorkshire Hospitals
NHS Trust
• South East Thames – Guy’s and St Thomas’
Hospital NHS Foundation Trust
• Kent-Sussex and Surrey – Queen Victoria
Hospital NHS Foundation Trust
• North Trent – Sheffield Teaching Hospitals NHS
Foundation Trust
Recently, the Royal College of Surgeons of England
(RCSE) has accredited a number of advanced post-
CCT head and neck fellowships. These posts are
funded by the individual hospitals but are accredited
by the RCSE. These include the advanced head and
neck surgery fellowship at Guy’s and St Thomas’
Hospital and another one at Charing Cross Hospital.5
In addition, there are several hospitals that offer further
advanced independent post-CCT HNSO fellowships
although these are yet to be recognised by accredited
bodies. These programmes are currently available in
University Hospital Birmingham, Addenbrooke’s
Hospital Cambridge, Aintree University Hospitals,
Liverpool, Nottingham University Hospital, and St
George’s Hospital in London.
In the European Union, subspecialty training in
HNSO remains diverse.6 However, the Union of
European Medical Specialists has initiated steps to
standardise subspecialty training in the EU and this is
likely to have an impact on the current training structure
in the near future. Currently, it is recommended that trai-
nees applying for head and neck surgical oncology posts
have the required additional and adequate training in this
subspecialty. This is often an essential or a desired
requirement in the job descriptions.
EDUCATION OF TRAINEES, TRAINING AND FELLOWSHIPS: UK GUIDELINES
Recommendation
• Trainees applying for Head and Neck
Surgical Oncology consultant posts should
have completed additional training in the
subspecialty
Key points
• Current Educational Programmes consist of an
aim, a syllabus, an assessment matrix and a
process for evaluation
• Trainees applying for Head and Neck Surgical
Oncology posts should have completed additional
training in the subspecialty
• Interface Surgical Fellowships and advanced Post
CCT Fellowships are currently available in the UK
as part of additional training in Head and Neck
Surgical Oncology
• In Clinical and Medical Oncology there are no
dedicated Fellowships for additional training.
S221
References
1 Joint Committee on Surgical Training. Intercollegiate Surgical
Curriculum Programme. https://www.iscp.ac.uk/ (accessed 15
November 2015)
2 The Royal College of Radiologists. Clinical Oncology. http://
www.rcr.ac.uk (accessed 15 November 2015)
3 Joint Royal Colleges of Physicians Training Board. Medical
Oncology. http://www.jrcptb.org.uk/specialties/medical-oncol-
ogy (accessed 15 November 2015)
4 Joint Committee on Surgical Training. Head and Neck Surgical
Oncology. http://www.jcst.org/training-interface-groups/head-
and-neck-surgical-oncology (accessed 15 November 2015)
5 Royal College of Surgeons. National Fellowship Register. https://
www.rcseng.ac.uk/surgeons/training/fellowships/national-fel
lowship-register/otolaryngology (accessed 15 November 2015)
6 Manganaris A, Black M, Balfour A, Hartley C, Jeannon JP, Simo R.
Sub-specialty training in head and neck surgical oncology in the
European Union. Eur Arch Otorhinolaryngol 2009;266:1005–10
Address for correspondence:
Ricard Simo,
Department of Otolaryngology – Head and Neck Surgery,
Guy’s and St Thomas’ Hospital NHS Foundation Trust,
Guy’s, King’s and St Thomas’ Medical and Dental School,
London, UK
E-mail: ricardsimo1@icloud.com
The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S222–S224. GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
reproduction in any medium, provided the original work is properly cited.
doi:10.1017/S0022215116000682

Future perspectives: United Kingdom National

Multidisciplinary Guidelines

E V KING1, K HARRINGTON2
1
Consultant Head and Neck Surgeon Poole Hospital NHS Foundation Trust and University of Southampton,
Southampton, UK, and 2Targeted Therapy Team, The Institute of Cancer Research, London, UK

Abstract
The multidisciplinary management of head and cancer has changed radically in the last decade. This paper provides
a glimpse of the emerging surgical and oncological interventions that may play major roles in the treatment
paradigms of tomorrow.

Surgery HPV-driven head and neck SCC than cervical cancer.1

Advances in surgical techniques appear slow and cum-
bersome compared with the rapid unravelling of
molecular mechanisms responsible for head and neck
squamous cell carcinoma (SCC). It is now clear that
head and neck SCC can be sub-divided into two
main cohorts, those that are driven by human papilloma
virus (HPV), and those that are not. This is only the first
level of patient stratification on our way to personalised
medicine. However, it provides a sensible basis for trial
recruitment, which is a good starting point.
It is clear that the majority of HPV-driven head and
neck SCC patients do well, irrespective of treatment.
This is in stark contrast to those patients who have
developed a tumour secondary to tobacco and alcohol
use, who may only have a 5 per cent survival advantage
compared to those patients treated over 20 years ago
with the same disease. Clearly, this heterogeneous
group deserves better outcomes, not just in terms of
survival, but also functional outcome improvement.
Trials now capture data relating to swallow (i.e.
PATHOS in HPV-positive disease), revealing the
change in concern regarding treatment-associated mor-
bidity. Ideally, this would also be reflected in ongoing
national data collection, formerly Data for Head and
Neck Oncology (DAHNO), to be replaced by Head
and Neck Cancer Audit (HANA).
Despite the incidence of some head and neck SCCs
decreasing over time (i.e. larynx), these numbers are
outweighed by the continued increase in other sub-
types, specifically oropharynx (Cancer Research
UK). This undoubtedly has economic implications as
combined head and neck clinics see more patients
year on year, often without additional clinical support.
It is predicted that by 2020 there will be more cases of
Will the prophylactic HPV vaccine slow the trend?
Despite not being introduced to address head and
neck SCC, it undoubtedly should have an effect.
There are ongoing discussions regarding vaccinating
boys, to fall in line with Australia, the USA, Austria
and parts of Canada, in view of the strong male predis-
position to HPV-driven head and neck SCC. The argu-
ments not to vaccinate boys relate to the short-term
cost implications, which in many countries has been
shown to be unsubstantiated,2–4 and the absence of evi-
dence of efficacy of the vaccine against oropharyngeal
disease.
Surgical instruments have continued to evolve and
many teams use lasers and harmonic scalpels routinely.
Some units use robotic surgery as part of their surgical
approach, with an evolving body of non-randomised
data to support its use.5,6 Long-term functional
outcome data are still lacking with this new technology,
but should be collected as a matter of course to ensure
both survival outcomes and functional morbidity con-
tinue to improve.
Novel tools to improve the certainty of surgical
resection margins intra-operatively are available in
theatre, ranging from the use of Lugol’s Iodine
(LIHNCS – Lugol’s Iodine in Head and Neck
Cancer Surgery) to commercially available systems
(PENTAX i-SCAN™, OLYMPUS narrow band
imaging and STORZ spies™). Cutting edge molecular
diagnostic tools (iKnife) require prospective data col-
lection to support their use, but if confirmed may revo-
lutionise the need for intra-operative frozen sections,
with significant cost-saving associations.7
Advances in microvascular techniques push the limit
of surgical resections, maximising the chances of
FUTURE PERSPECTIVES: UK GUIDELINES
surgical clearance and the associated links with
improved survival. In addition, microsurgical techni-
ques are being employed to reduce tumour- and/or
treatment-associated morbidity, examples including
complex nasal, midface and mandibular reconstruction,
most of which benefit from computer-aided planning to
fit individual defects and laryngeal re-innervation.
Imaging modalities continue to evolve and help
facilitate patient selection and operative limits. Recent
results from the positron emission tomography-Neck
trial will undoubtedly influence neck management
and future surveillance imaging, but this will require
backing from the Royal College of Radiologists to
support the change in clinical practice. Other avenues
that may provide enhanced imaging techniques
include dual-energy computed tomography (CT).8
Finally, surgeons are well placed to talk to patients
about research trials, even if it is just a matter of
taking consent to send tumour to the tissue bank.
Research is fundamental to improve our understanding
and treatment of this disease.
Oncology
There have been significant recent advances in non-sur-
gical oncological management of head and neck SCC.
These developments are likely to continue to shape our
thinking over the next decade as we develop more
effective, less toxic treatments for head and neck
SCC. The key themes are discussed below.
Improved radiotherapy (RT) techniques
In comparison with treatment techniques that would
have been standards of care one or two decades ago,
the current routine daily practice of RT is completely
unrecognisable. Three-dimensional conformal RT and
intensity-modulated radiotherapy are now considered
to be gold-standard treatments and are available in
almost every centre in the UK. Even these approaches
are being refined further with increasing application of
image-guided RT. This involves using imaging investi-
gations performed during a course of treatment to allow
oncologists to adapt the RT plan to ensure adequate
coverage of target volumes that contain (or may
contain) cancer cells while, at the same time, sparing
normal tissues. Increasing availability of linear accelera-
tors with on-board cone-beam CT and technologies that
allow fusion of planning CT scans with diagnostic mag-
netic resonance imaging scans will continue to drive this
process. In addition, the development of newer tech-
nologies, such as the MR-Linac and proton beam
therapy, means that the next decade is likely to see sig-
nificant advances in the therapeutic index of RT.9,10
Development of molecularly targeted radiosensitisers
As a result of meta-analyses of a large number of small-
to medium-sized randomised trials, we now recognise
RT delivered with concomitant platinum monotherapy
as a standard of care for unresected, locally advanced
head and neck SCC. A molecularly targeted antibody
S223
against epidermal growth factor receptor (EGFR),
cetuximab, has also been shown to enhance the effect
of RT in a single-phase III trial, but it did not yield add-
itional benefit when combined with platin-based che-
moradiotherapy.11 In the next decade, we are likely to
see a number of new targeted radiosensitisers devel-
oped for use in patients with head and neck SCC.
Improved understanding of key molecular events in
the response of cancer cells to radiation has highlighted
potential targets for developing tumour-selective radio-
sensitisers. In particular, dysregulated cell cycle control
and/or loss of key components of the DNA damage
response represent a molecular ‘Achilles’ heel’ that is
vulnerable to therapeutic exploitation with new agents
that include poly ADP ribose polymerase, Chk1, poly
ADP ribose polymerase and Wee1 kinase inhibitors.12
Development of immuno-oncology (I-O) agents
In recent years, I-O has emerged as a major new modal-
ity in the treatment of many solid cancers, including
head and neck SCC. This advance has been under-
pinned by huge strides in our understanding of the fun-
damental biological principles that guide the activity of
the immune system. In particular, specific immune
checkpoints have been discovered that are central com-
ponents of normal immune responses. In health, such
checkpoints function to inhibit T cells and prevent
their chronic activation or misdirection against normal
tissues. Effectively, they function as negative regulators
or ‘brakes’ on the normal immune response. Many
cancers subvert these inhibitory pathways in order to
escape from immunosurveillance by activating brakes
on the immune system. Immune checkpoint inhibitors
are able to release these brakes on the immune
system and trigger dramatic antitumour responses.
Antiprogrammed death (PD)-1 and anti-PD ligand-1-
targeted monoclonal antibodies have already shown
activity in head and neck SCC13 and it is highly
likely that other, newer checkpoint-inhibiting drugs
will enter clinical practice in the next 5–10 years. It
is very probable that head and neck SCC will continue
to represent a promising target for such drugs.
Development of effective adjuvant therapies
Previous attempts to use adjuvant chemotherapy in
patients who had completed definitive treatment for
locally advanced head and neck cancer were focused
on cytotoxic chemotherapy and failed to demonstrate
any benefit. Subsequent research moved towards
assessment of small molecule inhibitors of growth
factor receptors. Recent data have shown that the dual
EGFR/human epidermal growth factor2 inhibitor,
lapatinib, does not improve outcomes of post-operative
chemoradiotherapy in patients judged to be at high risk
of disease recurrence.14 In ongoing studies, the irre-
versible inhibitor of EGFR, HER2 and HER4, afatinib,
is being tested as an adjuvant therapy in high-risk
patients after definitive chemoradiation (phase III
LUX2 study NCT 01345669) or after post-operative
S224
chemoradiotherapy (GORTEC 2010-02, EudraCT
2010-023265-22). The increased prominence of I-O
agents (vide supra) signifies that adjuvant trials of
such agents will be conducted in the coming years.
Hopefully, such studies will deliver a successful
outcome against locoregional and metastatic recurrence
of head and neck SCC.
Personalised treatment through molecular
classification
We have made major advances in our understanding of
cancer by examining the genetic nature of the disease
[The Cancer Genome Atlas Network, 201515]. Recent
reports have provided detailed analysis of the mutational
landscapes in different types of tumours and this work is
beginning to provide insights that are likely to guide
future therapeutic innovation. For example, the basis
of the biological differences between HPV-positive
and -negative cancers is clear when examining their dif-
ferent genetic profiles. The preponderance of inactivat-
ing events (mutations, epigenetic silencing) in the p53
pathway in HPV-negative disease contrasts strongly
with the frequency of wild-type (i.e. normal) p53 in
HPV-positive disease. In addition, specific abnormal-
ities (e.g. PIK3CA mutations) are more common in
HPV-positive disease and may be suitable targets for
the specific drug therapies. It is likely that we will see
further subcategorisation of head and neck SCC in the
next decade and that will be accompanied by personal-
isation of treatment for individual patients based on
the genetic content of their disease.
Key points
• Increased patient participation in clinical trials
• Patient stratification for personalisation of
treatment
• Improved imaging techniques
• Advances in surgical tools including robotic
surgery
• Improved outcomes through new radiotherapy
technologies
• Incorporation of immuno-oncology agents in
radical and palliative treatment approaches
• Development of effective post-radiotherapy/che-
moradiotherapy adjuvant treatments
References
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Kim E et al. Human papillomavirus and rising oropharyngeal
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4294–301
2 Chesson HW, Ekwueme DU, Saraiya M, Dunne EF, Markowitz
LE. The cost-effectiveness of male HPV vaccination in the
United States. Vaccine 2011;29:8443–50
3 Marty R, Roze S, Bresse X, Largeron N, Smith-Palmer J.
Estimating the clinical benefits of vaccinating boys and girls
against HPV-related diseases in Europe. BMC Cancer 2013;
13:10
4 Graham DM, Isaranuwatchai W, Habbous S, de Oliveira C3, Liu
G1, Siu LL et al. A cost-effectiveness analysis of human papil-
lomavirus vaccination of boys for the prevention of oropharyn-
geal cancer. Cancer 2015;121:1785–92
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Lawson G et al. Oncologic outcomes after transoral robotic
surgery: a multi-institutional study. JAMA Otolaryngol Head
Neck Surg 2015;141:1043–51
6 Weinstein GS, O’Malley BW Jr, Magnuson JS, Carroll WR,
Olsen KD, Daio L et al. Transoral robotic surgery: a multicenter
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Laryngoscope 2012;122:1701–7
7 Balog J, Sasi-Szabo L, Kinross J, Lewis MR, Muirhead LJ,
Veselkov K et al. Intraoperative tissue identification using
rapid evaporative ionization mass spectrometry. Sci Transl
Med 2013;5:194–3
8 Vogl TJ, Schulz B, Bauer RW, Stover T, Sader R, Tawfik AM.
Dual-energy CT applications in head and neck imaging. AJR Am
J Roentgenol 2012;199:S34–9
9 Gregoire V, Langendijk JA, Nuyts S. Advances in Radiotherapy
for Head and Neck Cancer. J Clin Oncol 2015;33:3277–84
10 Raaymakers BW, Lagendijk JJ, Overweg J, Kok JG,
Raaijmakers AJ, Kerkhof EM et al. Integrating a 1.5T MRI
scanner with a 6 MV accelerator: proof of concept. Phys Med
Biol 2009;54:N229–37
11 Ang KK, Zhang Q, Rosenthal DI et al. Randomized phase III
trial of concurrent accelerated radiation plus cisplatin with or
without cetuximab for stage III to IV head and neck carcinoma:
RTOG 0522. J Clin Oncol 2014;32:2940–50
12 Dillon MT, Good JS, Harrington KJ. Selective targeting of the
G2/M cell cycle checkpoint to improve the therapeutic index
of radiotherapy. Clin Oncol (R Coll Radiol) 2014;26:257–65
13 Seiwert TY, Haddad RI, Gupta S et al. Antitumor activity and
safety of pembrolizumab in patients (pts) with advanced squa-
mous cell carcinoma of the head and neck (SCCHN): prelimin-
ary results from KEYNOTE-012 expansion cohort. J Clin Oncol
2015;33(suppl):abstr LBA6008
14 Harrington K, Temam S, Mehanna H, D’Cruz A, Jain M,
D’Onofrio I et al. Postoperative adjuvant lapatinib and concur-
rent chemoradiotherapy followed by maintenance lapatinib
monotherapy in high-risk patients with resected squamous cell
carcinoma of the head and neck: a phase III, randomized,
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Address for correspondence:
E. King,
Poole Hospital NHS Foundation Trust,
University of Southampton,
Southampton, UK
E-mail: e.king@soton.ac.uk
00222151_130-S2_00222151_130-S2 06/05/16 12:05 PM Page 2
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00222151_130-S2_00222151_130-S2 06/05/16 12:05 PM Page 1

The Journal of
Laryngology & Otology VOLUME 130 MAY 2016 VOLUME 130 | NUMBER S2 | MAY 2016 ISSN: 0022-2151

Foreword S1

The Journal of Laryngology & Otology

Guidelines
Introduction to the United Kingdom National Multidisciplinary Guidelines for Head and Neck Cancer: V Paleri, N Roland
Organisation and provision of head and neck cancer surgical services in the United Kingdom: United Kingdom National Multidisciplinary Guidelines:
S3
The Journal of
F Stafford, K Ah-See, M Fardy, K Fell S5

Laryngology
Aetiology and risk factors for head and neck cancer: United Kingdom National Multidisciplinary Guidelines: R Shaw, N Beasley S9
Pre-treatment clinical assessment in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: A Robson, J Sturman,
P Williamson, P Conboy, S Penney, H Wood S13
Anaesthesia for head and neck surgery: United Kingdom National Multidisciplinary Guidelines: P Charters, I Ahmad, A Patel, S Russell S23
Imaging in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: H Lewis-Jones, S Colley, D Gibson S28
Nutritional management in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: B Talwar, R Donnelly, R Skelly, M Donaldson S32

& Otology
Restorative dentistry and oral rehabilitation: United Kingdom National Multidisciplinary Guidelines: C Butterworth, L McCaul, C Barclay S41
Psychological management for head and neck cancer patients: United Kingdom National Multidisciplinary Guidelines: G Humphris S45
Quality of life considerations in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: SN Rogers, C Semple, M Babb, G Humphris S49
Tumour assessment and staging: United Kingdom National Multidisciplinary Guidelines: N Roland, G Porter, B Fish, Z Makura S53
Pathological aspects of the assessment of head and neck cancers: United Kingdom National Multidisciplinary Guidelines: TR Helliwell, TE Giles S59
Radiotherapy in head and neck cancer management: United Kingdom National Multidisciplinary Guidelines: C Nutting S66
Surgery in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: JJ Homer S68
Chemotherapy: United Kingdom National Multidisciplinary Guidelines: CG Kelly S71
Laryngeal cancer: United Kingdom National Multidisciplinary guidelines: TM Jones, M De, B Foran, K Harrington, S Mortimore S75
Oral cavity and lip cancer: United Kingdom National Multidisciplinary Guidelines: C Kerawala, T Roques, J-P Jeannon, B Bisase S83
Oropharyngeal cancer: United Kingdom National Multidisciplinary Guidelines: H Mehanna, M Evans, M Beasley, S Chatterjee, M Dilkes, J Homer, Head and Neck Cancer:
J O’hara, M Robinson, R Shaw, P Sloan S90
Nasopharyngeal carcinoma: United Kingdom National Multidisciplinary Guidelines: R Simo, M Robinson, M Lei, A Sibtain, S Hickey S97
United Kingdom National Multidisciplinary Guidelines
Hypopharyngeal cancer: United Kingdom National Multidisciplinary Guidelines: P Pracy, S Loughran, J Good, S Parmar, R Goranova S104 Edited by Vinidh Paleri and Nick Roland
Nose and paranasal sinus tumours: United Kingdom National Multidisciplinary Guidelines: VJ Lund, PM Clarke, AC Swift, GW McGarry,
C Kerawala, D Carnell S111
Management of lateral skull base cancer: United Kingdom National Multidisciplinary Guidelines: JJ Homer, T Lesser, D Moffat, N Slevin,
R Price, T Blackburn S119
Non-melanoma skin cancer: United Kingdom National Multidisciplinary Guidelines: C Newlands, R Currie, A Memon, S Whitaker, T Woolford S125
Head and neck melanoma (excluding ocular melanoma): United Kingdom National Multidisciplinary Guidelines: OA Ahmed, C Kelly S133
ENDORSED BY:

VOLUME 130 | NUMBER S2 | MAY 2016

Management of Salivary Gland Tumours: United Kingdom National Multidisciplinary Guidelines: S Sood, M McGurk, F Vaz S142
Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines: AL Mitchell, A Gandhi, D Scott-Coombes, P Perros S150
Management of neck metastases in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: V Paleri, TG Urbano, H Mehanna, British Association of Endocrine and
C Repanos, J Lancaster, T Roques, M Patel, M Sen S161
Thyroid Surgeons (BAETS)
Investigation and management of the unknown primary with metastatic neck disease: United Kingdom National Multidisciplinary Guidelines: K Mackenzie,
M Watson, P Jankowska, S Bhide, R Simo S170
Speech and swallow rehabilitation in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: P Clarke, K Radford, M Coffey, British Association of Head and Neck
M Stewart S176
Recurrent head and neck cancer: United Kingdom National Multidisciplinary Guidelines: H Mehanna, A Kong, SK Ahmed S181
Oncologists (BAHNO)
Reconstructive considerations in head and neck surgical oncology: United Kingdom National Multidisciplinary Guidelines: M Ragbir, JS Brown, H Mehanna S191
Palliative and supportive care in head and neck cancer: United Kingdom National Multidisciplinary Guidelines: H Cocks, K Ah–See, M Capel, P Taylor S198 British Association of Oral and
Follow-up after treatment for head and neck cancer: United Kingdom National Multidisciplinary Guidelines: R Simo, J Homer, P Clarke, K Mackenzie, Maxillofacial Surgeons (BAOMS)
V Paleri, P Pracy, N Roland S208
The clinical nurse specialist’s role in head and neck cancer care: United Kingdom National Multidisciplinary Guidelines: L Dempsey, S Orr, S Lane, A Scott S212
Clinical research, national studies and grant applications: United Kingdom National Multidisciplinary Guidelines: N Stafford S216 British Association of
Education of trainees, training and fellowships for head and neck oncologic and surgical training in the UK: United Kingdom National Otorhinolaryngology–Head and
Multidisciplinary Guidelines: R Simo, A Robson, B Woodwards, P Niblock, P Matteucci S218
Future perspectives: United Kingdom National Multidisciplinary Guidelines: EV King, K Harrington S222 Neck Surgery (ENT UK)

British Association of Plastic,

Reconstructive and Aesthetic Surgeons
(BAPRAS)

The Royal College of Pathologists

(RCPath)

The Royal College of Radiologists

(Faculty of Clinical Oncology) (RCR)
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